Anti-BDCA2 antibody and use thereof

Abstract

The present disclosure relates to an anti-BDCA2 antibody and a use thereof. Specifically, the present disclosure relates to an anti-BDCA2 antibody or an antigen-binding fragment thereof, a nucleic acid encoding same, a pharmaceutical composition comprising same, and a use thereof in the treatment of diseases.

Description

Anti-bdca2 antibodies and uses thereof TECHNICAL FIELD

[0001] The present disclosure relates to the field of biomedicine, in particular to an anti-BDCA2 antibody and use thereof as a drug. BACKGROUND

[0002] Human plasmacytoid dendritic cells (pDCs) are part of the innate immune system, which recognize pathogen-associated molecules through TLR7 and TLR9 to secrete abundant type I interferons and trigger the activation of various immune cells such as NK cells, B cells and T cells, and initiate adaptive immunity. pDCs are the main source of type I interferon secretion, and in pathological conditions, pDCs can produce a large amount of type I interferon to participate in the occurrence and development of autoimmune diseases, such as lupus erythematosus SLE / CLE, scleroderma SSc and psoriasis, etc.

[0003] BDCA2 (Blood dendritic cell antigen 2) is also known as CLEC4C or CD303, which belongs to the C-type lectin family. BDCA2 is specifically expressed on the surface of pDCs, and the intracellular region binds FcεR Iγ to transmit signals and induce BCR (B cell antigen receptor) like signal transduction cascade, which has a negative regulatory effect on the production of type I interferon. The antibody against BDCA2 can bind to BDCA2, thereby down-regulating the production of type I interferon and other cytokines, so as to achieve the purpose of treating autoimmune diseases (such as lupus erythematosus).

[0004] At present, there is no antibody against BDCA2 on the market, and it is still necessary to develop new effective BDCAD2 antibodies to meet the clinical needs. SUMMARY

[0005] In a first aspect, the present disclosure provides an anti-BDCA2 antibody or an antigen binding fragment thereof.

[0006] Specifically, the anti-BDCA2 antibody or the antigen binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein

[0007] a) the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 in any one of SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56 and SEQ ID NO: 57; and

[0008] the light chain variable region comprises LCDR1, LCDR2, and LCDR3 in any one of SEQ ID NO: 61, SEQ ID NO: 25, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64;

[0009] b) the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 in any one of SEQ ID NO: 31, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30; and

[0010] the light chain variable region comprises LCDR1, LCDR2, and LCDR3 in any one of SEQ ID NO: 38, SEQ ID NO: 21, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42; or

[0011] c) the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47; and

[0012] the light chain variable region comprises LCDR1, LCDR2, and LCDR3 in any one of SEQ ID NO: 49, SEQ ID NO: 23, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 51, and SEQ ID NO: 52.

[0013] In a specific embodiment, the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 in the sequence of SEQ ID NO: 58; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 in the sequence of SEQ ID NO: 61.

[0014] In a specific embodiment, the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 in the sequence of SEQ ID NO: 31; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 in the sequence of SEQ ID NO: 38.

[0015] In particular embodiments, the heavy chain variable region comprises a HCDR1, a HCDR2, and a HCDR3 in the sequence of SEQ ID NO: 43; and the light chain variable region comprises a LCDR1, a LCDR2, and a LCDR3 in the sequence of SEQ ID NO: 49.

[0016] In particular embodiments, the amino acid sequences of the HCDRs and the LCDRs are determined according to the Kabat, Chothia, AbM, or IMTG numbering system.

[0017] In particular embodiments, the amino acid sequences of the HCDRs and the LCDRs are determined according to the Kabat numbering system.

[0018] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0019] the heavy chain variable region comprises a HCDR1 of SEQ ID NO: 14, a HCDR2 of SEQ ID NO: 84, and a HCDR3 of SEQ ID NO: 16; wherein

[0020] SEQ ID NO: 84 has the general formula TISSGX 13 X 14 YTYYPX 15 SVKG, wherein X 13 is selected from D or E, X 14 is selected from S or A, X 15 is selected from D or E; and

[0021] the light chain variable region comprises a LCDR1 of SEQ ID NO: 85, a LCDR2 of SEQ ID NO: 18, and a LCDR3 of SEQ ID NO: 19; wherein

[0022] SEQ ID NO: 85 has the general formula KASESVDYX 16 X 17 ESYVN, wherein X 16 is selected from D or E, X 17 is selected from G or A.

[0023] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0024] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in any one of SEQ ID NO: 76, SEQ ID NO: 15, and SEQ ID NO: 75, and HCDR3 set forth in SEQ ID NO: 16; and

[0025] the light chain variable region comprises LCDR1 set forth in any one of SEQ ID NO: 77, SEQ ID NO: 17, and SEQ ID NO: 78, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19.

[0026] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0027] i) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0028] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 77, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0029] ii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0030] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 17, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0031] iii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0032] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: SEQ ID NO: 78, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0033] iv) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 15, and HCDR3 set forth in SEQ ID NO: 16; and

[0034] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 77, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0035] v) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 15, and HCDR3 set forth in SEQ ID NO: 16; and

[0036] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 17, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0037] vi) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 15, and HCDR3 set forth in SEQ ID NO: 16; and

[0038] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 78, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19; or

[0039] vii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 75, and HCDR3 set forth in SEQ ID NO: 16; and

[0040] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 17, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0041] viii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 75, and HCDR3 set forth in SEQ ID NO: 16; and

[0042] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 77, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0043] ix) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 75, and HCDR3 set forth in SEQ ID NO: 16; and

[0044] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 78, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19.

[0045] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein:

[0046] a-1) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0047] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 77, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0048] a-2) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 75, and HCDR3 set forth in SEQ ID NO: 16; and

[0049] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 17, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0050] a-3) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0051] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 17, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19;

[0052] a-4) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 15, and HCDR3 set forth in SEQ ID NO: 16; and

[0053] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0054] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0055] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0056] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region and a light chain variable region, wherein:

[0057] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0058] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and

[0059] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region and a light chain variable region; wherein:

[0060] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 79, and HCDR3 set forth in SEQ ID NO: 4; wherein

[0061] SEQ ID NO: 79 has the general formula SVSSGGSSTYYPX1X2VKG, wherein X1 is selected from D or E, and X2 is selected from S or A; and

[0062] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 79, and HCDR3 set forth in SEQ ID NO: 4; wherein

[0063] SEQ ID NO: 80 has the general formula X3ASQSVDYX4GX5X6YMN, wherein X3 is selected from K or R, X4 is selected from D or E, X5 is selected from D or E, and X6 is selected from S or A; and

[0064] SEQ ID NO: 81 has the general formula TASNX7EX8, wherein X7 is selected from L or K, and X8 is selected from S or T.

[0065] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0066] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in any one of SEQ ID NO: 3, SEQ ID NO: 65, and SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0067] the light chain variable region comprises LCDR1 set forth in any one of SEQ ID NO: 5, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, and SEQ ID NO: 70, LCDR2 set forth in SEQ ID NO: 6 or SEQ ID NO: 71, and LCDR3 set forth in SEQ ID NO: 7.

[0068] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0069] i) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 3, and HCDR3 set forth in SEQ ID NO: 4; and

[0070] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 5, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0071] ii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 3, and HCDR3 set forth in SEQ ID NO: 4; and

[0072] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 67, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0073] iii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 3, and HCDR3 set forth in SEQ ID NO: 4; and

[0074] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 68, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0075] iv) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 3, and HCDR3 set forth in SEQ ID NO: 4; and

[0076] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 69, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0077] v) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 3, and HCDR3 set forth in SEQ ID NO: 4; and

[0078] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 70, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0079] vi) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 3, and HCDR3 set forth in SEQ ID NO: 4; and

[0080] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 70, LCDR2 set forth in SEQ ID NO: 71, and LCDR3 set forth in SEQ ID NO: 7;

[0081] vii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 65, and HCDR3 set forth in SEQ ID NO: 4; and

[0082] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 68, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0083] viii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 65, and HCDR3 set forth in SEQ ID NO: 4; and

[0084] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 69, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0085] ix) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 65, and HCDR3 set forth in SEQ ID NO: 4; and

[0086] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 70, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0087] x) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 65, and HCDR3 set forth in SEQ ID NO: 4; and

[0088] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 70, LCDR2 set forth in SEQ ID NO: 71, and LCDR3 set forth in SEQ ID NO: 7;

[0089] xi) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 65, and HCDR3 set forth in SEQ ID NO: 4; and

[0090] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 5, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0091] xii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0092] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 68, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0093] xiii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0094] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 69, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0095] xiv) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0096] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 70, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0097] xv) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0098] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 70, LCDR2 set forth in SEQ ID NO: 71, and LCDR3 set forth in SEQ ID NO: 7;

[0099] xvi) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0100] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 5, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0101] xvii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 65, and HCDR3 set forth in SEQ ID NO: 4; and

[0102] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 67, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7;

[0103] xviii) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 2, HCDR2 as set forth in SEQ ID NO: 65, and HCDR3 as set forth in SEQ ID NO: 4; and

[0104] the light chain variable region comprises LCDR1 as set forth in SEQ ID NO: 67, LCDR2 as set forth in SEQ ID NO: 6, and LCDR3 as set forth in SEQ ID NO: 7;

[0105] xix) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 2, HCDR2 as set forth in SEQ ID NO: 65, and HCDR3 as set forth in SEQ ID NO: 4; and

[0106] the light chain variable region comprises LCDR1 as set forth in SEQ ID NO: 5, LCDR2 as set forth in SEQ ID NO: 71, and LCDR3 as set forth in SEQ ID NO: 7;

[0107] xx) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 2, HCDR2 as set forth in SEQ ID NO: 66, and HCDR3 as set forth in SEQ ID NO: 4; and

[0108] the light chain variable region comprises LCDR1 as set forth in SEQ ID NO: 5, LCDR2 as set forth in SEQ ID NO: 71, and LCDR3 as set forth in SEQ ID NO: 7; or

[0109] xxi) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 2, HCDR2 as set forth in SEQ ID NO: 3, and HCDR3 as set forth in SEQ ID NO: 4; and

[0110] the light chain variable region comprises LCDR1 as set forth in SEQ ID NO: 5, LCDR2 as set forth in SEQ ID NO: 71, and LCDR3 as set forth in SEQ ID NO: 7.

[0111] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0112] b-1) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 2, HCDR2 as set forth in SEQ ID NO: 66, and HCDR3 as set forth in SEQ ID NO: 4; and

[0113] the light chain variable region comprises a LCDR1 of SEQ ID NO: 68, a LCDR2 of SEQ ID NO: 6, and a LCDR3 of SEQ ID NO: 7;

[0114] b-2) the heavy chain variable region comprises a HCDR1 of SEQ ID NO: 2, a HCDR2 of SEQ ID NO: 3, and a HCDR3 of SEQ ID NO: 4; and

[0115] the light chain variable region comprises a LCDR1 of SEQ ID NO: 67, a LCDR2 of SEQ ID NO: 6, and a LCDR3 of SEQ ID NO: 7;

[0116] b-3) the heavy chain variable region comprises a HCDR1 of SEQ ID NO: 2, a HCDR2 of SEQ ID NO: 3, and a HCDR3 of SEQ ID NO: 4; and

[0117] the light chain variable region comprises a LCDR1 of SEQ ID NO: 69, a LCDR2 of SEQ ID NO: 6, and a LCDR3 of SEQ ID NO: 7;

[0118] b-4) the heavy chain variable region comprises a HCDR1 of SEQ ID NO: 2, a HCDR2 of SEQ ID NO: 3, and a HCDR3 of SEQ ID NO: 4; and

[0119] the light chain variable region comprises a LCDR1 of SEQ ID NO: 70, a LCDR2 of SEQ ID NO: 71, and a LCDR3 of SEQ ID NO: 7;

[0120] b-5) the heavy chain variable region comprises a HCDR1 of SEQ ID NO: 2, a HCDR2 of SEQ ID NO: 65, and a HCDR3 of SEQ ID NO: 4; and

[0121] the light chain variable region comprises a LCDR1 of SEQ ID NO: 68, a LCDR2 of SEQ ID NO: 6, and a LCDR3 of SEQ ID NO: 7;

[0122] b-6) the heavy chain variable region comprises a HCDR1 of SEQ ID NO: 2, a HCDR2 of SEQ ID NO: 65, and a HCDR3 of SEQ ID NO: 4; and

[0123] the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 69, a LCDR2 as set forth in SEQ ID NO: 6, and a LCDR3 as set forth in SEQ ID NO: 7;

[0124] b-7) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 65, and a HCDR3 as set forth in SEQ ID NO: 4; and

[0125] the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 70, a LCDR2 as set forth in SEQ ID NO: 71, and a LCDR3 as set forth in SEQ ID NO: 7;

[0126] b-8) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 65, and a HCDR3 as set forth in SEQ ID NO: 4; and

[0127] the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 5, a LCDR2 as set forth in SEQ ID NO: 6, and a LCDR3 as set forth in SEQ ID NO: 7;

[0128] b-9) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 3, and a HCDR3 as set forth in SEQ ID NO: 4; and

[0129] the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 5, a LCDR2 as set forth in SEQ ID NO: 6, and a LCDR3 as set forth in SEQ ID NO: 7;

[0130] b-10) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 66, and a HCDR3 as set forth in SEQ ID NO: 4; and

[0131] the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 69, a LCDR2 as set forth in SEQ ID NO: 6, and a LCDR3 as set forth in SEQ ID NO: 7;

[0132] b-11) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 66, and a HCDR3 as set forth in SEQ ID NO: 4; and

[0133] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0134] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0135] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0136] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region and a light chain variable region; wherein:

[0137] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0138] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0139] SEQ ID NO: 82 has the general formula X9ASQSVDYX 10 GDNYIN, wherein X9is selected from K or R, X 10 is selected from D or E; and

[0140] SEQ ID NO: 83 has the general formula TASNX 11 DX 12 , wherein X 11 is selected from L or K, X 12 is selected from S or T.

[0141] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain variable region and a light chain variable region; wherein:

[0142] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and

[0143] the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO:8, HCDR2 set forth in SEQ ID NO:9, and HCDR3 set forth in SEQ ID NO: 10; and

[0144] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0145] i) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO:8, HCDR2 set forth in SEQ ID NO:9, and HCDR3 set forth in SEQ ID NO: 10; and

[0146] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 11, LCDR2 set forth in SEQ ID NO: 12, and LCDR3 set forth in SEQ ID NO: 13;

[0147] ii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO:8, HCDR2 set forth in SEQ ID NO:9, and HCDR3 set forth in SEQ ID NO: 10; and

[0148] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 11, LCDR2 set forth in SEQ ID NO: 74, and LCDR3 set forth in SEQ ID NO: 13;

[0149] iii) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO:8, HCDR2 set forth in SEQ ID NO:9, and HCDR3 set forth in SEQ ID NO: 10; and

[0150] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 72, LCDR2 set forth in SEQ ID NO: 12, and LCDR3 set forth in SEQ ID NO: 13;

[0151] iv) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO:8, HCDR2 set forth in SEQ ID NO:9, and HCDR3 set forth in SEQ ID NO: 10; and

[0152] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 73, LCDR2 set forth in SEQ ID NO: 74, and LCDR3 set forth in SEQ ID NO: 13; or

[0153] v) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 8, HCDR2 set forth in SEQ ID NO: 9, and HCDR3 set forth in SEQ ID NO: 10; and

[0154] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 73, LCDR2 set forth in SEQ ID NO: 12, and LCDR3 set forth in SEQ ID NO: 13.

[0155] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0156] c-1) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 8, HCDR2 set forth in SEQ ID NO: 9, and HCDR3 set forth in SEQ ID NO: 10; and

[0157] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 11, LCDR2 set forth in SEQ ID NO: 12, and LCDR3 set forth in SEQ ID NO: 13;

[0158] c-2) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 8, HCDR2 set forth in SEQ ID NO: 9, and HCDR3 set forth in SEQ ID NO: 10; and

[0159] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 72, LCDR2 set forth in SEQ ID NO: 12, and LCDR3 set forth in SEQ ID NO: 13; or

[0160] c-3) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 8, HCDR2 set forth in SEQ ID NO: 9, and HCDR3 set forth in SEQ ID NO: 10; and

[0161] the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 73, LCDR2 set forth in SEQ ID NO: 74, and LCDR3 set forth in SEQ ID NO: 13.

[0162] The HCDRs and LCDRs as described above are determined according to the Kabat numbering system.

[0163] In particular embodiments, the anti-BDCA2 antibody of the present disclosure is a murine, chimeric, or humanized antibody.

[0164] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0165] the heavy chain variable region comprises the amino acid sequence set forth in any one of SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57, or an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57; and

[0166] the light chain variable region comprises the amino acid sequence set forth in any one of SEQ ID NO: 61, SEQ ID NO: 25, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64, or an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 61, SEQ ID NO: 25, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64.

[0167] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0168] the heavy chain variable region comprises an amino acid sequence set forth in any one of SEQ ID NO: 58, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 58, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57; and

[0169] the light chain variable region comprises an amino acid sequence set forth in any one of SEQ ID NO: 61, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 61, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64.

[0170] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0171] the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO: 24, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 24; and

[0172] The heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 58, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 58; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 61, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 61.

[0173] In particular embodiments, an anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0174] a-1) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 58, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 58; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 61, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 61;

[0175] a-2) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 53, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 53; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 59;

[0176] a-3) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 53, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 53; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 60, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 60;

[0177] a-4) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 54, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 54; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 59;

[0178] a-5) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 54, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 54; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 60, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 60;

[0179] a-6) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 55, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 55; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 59;

[0180] a-7) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 55, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 55; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 60, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 60;

[0181] a-8) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 56, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 56; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 59;

[0182] a-9) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:56, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:56; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:60, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:60;

[0183] a-10) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:57, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:59, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:59;

[0184] a-11) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:57, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:60, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:60;

[0185] a-12) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:57, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:61, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:61;

[0186] a-13) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:57, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:62, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:62;

[0187] a-14) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:57, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:63, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:63;

[0188] a-15) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:57, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:64, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:64;

[0189] a-16) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:58, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:58; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:62, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:62;

[0190] a-17) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:24, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:24; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:25, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:25;

[0191] a-18) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 53, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 53; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 61, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 61;

[0192] a-19) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 53, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 53; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 62, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 62;

[0193] a-20) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 56, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 56; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 61, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 61; or

[0194] a-21) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:56, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:56; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:62, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:62.

[0195] In particular embodiments, an anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0196] the heavy chain variable region comprises an amino acid sequence as set forth in any one of SEQ ID NO:31, SEQ ID NO:20, SEQ ID NO:28, SEQ ID NO:29, and SEQ ID NO:30, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence as set forth in any one of SEQ ID NO:31, SEQ ID NO:20, SEQ ID NO:28, SEQ ID NO:29, and SEQ ID NO:30; and

[0197] the heavy chain variable region comprises an amino acid sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30; and

[0198] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0199] the heavy chain variable region comprises an amino acid sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30; and

[0200] the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 20, or comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 20; and

[0201] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0202] the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 20, or comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 20; and

[0203] the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 21, or comprises an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 21.

[0204] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0205] b-1) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:31, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:31; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:38, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:38;

[0206] b-2) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:28, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:28; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:32, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:32;

[0207] b-3) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:28, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:28; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:33, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:33;

[0208] b-4) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 28, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 34, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 34;

[0209] b-5) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 28, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 35, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 35;

[0210] b-6) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 28, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 37, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 37;

[0211] b-7) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:28, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:39, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:39;

[0212] b-8) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:28, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:40, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:40;

[0213] b-9) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:28, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:41, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:41;

[0214] b-10) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 32, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 32;

[0215] b-11) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 33, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 33;

[0216] b-12) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 34, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 34;

[0217] b-13) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 35, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 35;

[0218] b-14) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 36, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 36;

[0219] b-15) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 30; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 38, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 38;

[0220] b-16) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 30, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 30; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 39, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 39;

[0221] b-17) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 30, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 30; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 40, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 40;

[0222] b-18) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 30, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 30; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 41, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 41;

[0223] b-19) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:31, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:31; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:39, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:39;

[0224] b-20) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:31, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:31; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:40, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:40;

[0225] b-21) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:31, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:31; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:41, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:41;

[0226] b-22) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:31, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:31; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:42, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:42;

[0227] b-23) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:28, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:38, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:38;

[0228] b-24) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:30, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:30; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:35, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:35;

[0229] b-25) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 31, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 31; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 35, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 35; or

[0230] b-26) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 20, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 20; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 21, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 21.

[0231] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0232] the heavy chain variable region comprises an amino acid sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47; and

[0233] the light chain variable region comprises an amino acid sequence set forth in any one of SEQ ID NO: 49, SEQ ID NO: 23, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 51, and SEQ ID NO: 52, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 49, SEQ ID NO: 23, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 51, and SEQ ID NO: 52.

[0234] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0235] the heavy chain variable region comprises an amino acid sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47; and the light chain variable region comprises an amino acid sequence set forth in any one of SEQ ID NO: 49, SEQ ID NO: 23, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 51, and SEQ ID NO: 52, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 49, SEQ ID NO: 23, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 51, and SEQ ID NO: 52.

[0236] the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 22; and

[0237] In particular embodiments, an anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0238] the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 22; and

[0239] the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 23.

[0240] In particular embodiments, an anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0241] c-1) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:43, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:43; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:49, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:49;

[0242] c-2) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:43, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:43; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:50, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:50;

[0243] c-3) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:44, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:44; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:48, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:48;

[0244] c-4) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:44, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:44; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:49, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:49;

[0245] c-5) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:44, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:44; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:50, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:50;

[0246] c-6) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:45, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:45; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:48, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:48;

[0247] c-7) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:45, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:45; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:49, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:49;

[0248] c-8) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:45, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:45; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:50, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:50;

[0249] c-9) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:46, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:46; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:51, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:51;

[0250] c-10) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:46, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:46; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:52, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:52;

[0251] c-11) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:47, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:47; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:51, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:51;

[0252] c-12) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:47, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:47; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO:52, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO:52; or

[0253] c-13) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 22; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 23, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 23.

[0254] In particular embodiments, an anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0255] the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 58, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 58; and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 61, or comprises an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 61.

[0256] In particular embodiments, an anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0257] the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 43, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 43; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 49, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 49.

[0258] In particular embodiments, an anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein:

[0259] the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 43, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 43; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 49, or an amino acid sequence that has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 49.

[0260] In particular embodiments, an anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein: the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 58 and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 61.

[0261] In particular embodiments, an anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein: the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 31 and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 38.

[0262] In a specific embodiment, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure comprises a heavy chain variable region and a light chain variable region; wherein: the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 43, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 49.

[0263] In a specific embodiment, the antigen-binding fragment of the anti-BDCA2 antibody of the present disclosure is selected from any one of the following: Fab, scFv, Fv, Fab', F(ab')2, single domain antibody, scFab, linear antibody, and multispecific antibody.

[0264] In a specific embodiment, the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure further comprises a heavy chain constant region and / or a light chain constant region.

[0265] In a specific embodiment, the heavy chain constant region of the present disclosure is selected from the constant region of human IgGl, human IgG2, human IgG3, and human IgG4, or a mutant thereof.

[0266] In a specific embodiment, the heavy chain constant region mutant comprises a mutation that prolongs the half-life of the antibody.

[0267] As known to those skilled in the art, Fc positions that can be mutated to prolong half-life (e.g., binding to FcRn) include positions 250, 252, 254, 256, 307, 380, 428, 434, and 435. Exemplary mutations that can be made individually or in combination are T250Q, M252Y, S254T, T256E, T307A, E380A, M428L, N434S, or N434A. Exemplary combination mutations are M428L / N434S, M252Y / S254T / T256E, T250Q / M428L, N434A, or T307A / E380A / N434A, where the amino acid residue numbering is according to the EU index.

[0268] In a specific embodiment, the heavy chain constant region mutant has a Y amino acid at position 252, a T amino acid at position 254, and an E amino acid at position 256.

[0269] In a specific embodiment, the heavy chain constant region mutant has an L amino acid at position 428 and an S amino acid at position 434, the amino acid positions being determined by EU numbering.

[0270] In a specific embodiment, the light chain constant region is selected from a lambda light chain constant region and a kappa light chain constant region.

[0271] In particular embodiments, the heavy chain constant region is the constant region of human IgGl or a mutant thereof comprising M252Y, S254T, and T256E mutations according to EU numbering.

[0272] In particular embodiments, the heavy chain constant region is the constant region of human IgGl or a mutant thereof comprising M428L and N434S mutations according to EU numbering.

[0273] In particular embodiments, the light chain constant region is the constant region of a kappa light chain.

[0274] In particular embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 26 or a mutant thereof comprising M252Y, S254T, and T256E mutations according to EU numbering, and the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 27.

[0275] In particular embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 26 or a mutant thereof comprising M428L and N434S mutations according to EU numbering, and the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 27.

[0276] In particular embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 93 and the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 27.

[0277] In particular embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 92 and the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 27.

[0278] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain and a light chain, wherein:

[0279] a-1) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 90, or an amino acid sequence having at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 90, and

[0280] the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 94, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 94, and

[0281] the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 94, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 94, and

[0282] the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 94, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 94, and

[0283] the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 94, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 94, and

[0284] the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 94, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 94, and

[0285] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain and a light chain, wherein:

[0286] b-1) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 86, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 86, and

[0287] the light chain comprises the amino acid sequence set forth in SEQ ID NO: 87, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 87;

[0288] b-2) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 97, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 97, and

[0289] the light chain comprises the amino acid sequence set forth in SEQ ID NO: 87, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 87; or

[0290] b-3) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 98, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 98, and

[0291] the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 88, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 88, and

[0292] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain and a light chain, wherein:

[0293] c-1) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 88, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 88, and

[0294] the light chain comprises the amino acid sequence set forth in SEQ ID NO: 89, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 89;

[0295] c-2) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 99, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 99, and

[0296] the light chain comprises the amino acid sequence set forth in SEQ ID NO: 89, or comprises an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 89; or

[0297] c-3) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 95, or an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 95, and

[0298] the light chain comprises the amino acid sequence set forth in SEQ ID NO: 89, or an amino acid sequence that has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 89.

[0299] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain and a light chain, wherein:

[0300] a-1) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 90 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 91;

[0301] a-2) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 94 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 91; or

[0302] a-3) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 96 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 91.

[0303] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure comprises a heavy chain and a light chain, wherein:

[0304] b-1) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 86 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 87;

[0305] b-2) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 97 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 87; or

[0306] b-3) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 98 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 87.

[0307] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided herein comprises a heavy chain and a light chain, wherein:

[0308] c-1) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 88, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 89;

[0309] c-2) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 99, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 89; or

[0310] c-3) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 95, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 89.

[0311] The anti-BDCA2 antibody or antigen-binding fragment thereof provided herein has any one or more of the following functional properties:

[0312] 1) binds to human or cynomolgus BDCA2 with high binding affinity;

[0313] 2) effectively inhibits TLR9-induced IFN-a secretion by PBMCs of healthy humans and SLE patients;

[0314] 3) effectively inhibits TLR7-induced IFN-a secretion by PBMCs of healthy humans and SLE patients;

[0315] 4) effectively inhibits immune complex-induced IFN-a secretion;

[0316] 5) can mediate killing of target cells (tumor cells) via ADCC activity; and

[0317] 6) high thermal stability.

[0318] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided herein has an EC50 value of less than 0.0024 pg / mL, e.g., 0.00037 pg / mL, for inhibiting TLR9-induced IFN-a secretion in PBMCs of healthy humans. The specific testing method can refer to Example 5.4.

[0319] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided herein mediates a maximum killing rate of HEK-hBDCA2 cells by ADCC activity of greater than 24%, e.g., 31%. The specific testing method can refer to Example 6.

[0320] In particular embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof provided by the present disclosure has a Tm value higher than 68°C, for example 78°C, as detected by the Nanotemper method. In particular, the detection method can refer to Example 7.

[0321] In a second aspect, there is provided a pharmaceutical composition comprising the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure, further comprising one or more pharmaceutically acceptable carriers, diluents, buffers or excipients.

[0322] In a third aspect, there is provided an isolated nucleic acid encoding the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure.

[0323] In a fourth aspect, there is provided an expression vector for expressing the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure, comprising a nucleic acid encoding the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure.

[0324] In a fifth aspect, there is provided a host cell for expressing the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure, which is transfected with the expression vector of the present disclosure.

[0325] In some embodiments, the host cell is prokaryotic, for example E. coli. In other embodiments, the host cell is eukaryotic, for example a HEK293 cell, a CHO cell, a yeast cell, or a plant cell.

[0326] In some embodiments, the host cell is incapable of developing into an individual.

[0327] In a sixth aspect, there is provided a method of treating and / or preventing a disease or disorder, comprising administering to a subject in need thereof a therapeutically or prophylactically effective amount of the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure, or the pharmaceutical composition of the present disclosure.

[0328] In a seventh aspect, there is provided the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure, or the pharmaceutical composition of the present disclosure, for use as a medicament. In particular embodiments, for use as a medicament for treating an inflammatory disease or an autoimmune disease.

[0329] In an eighth aspect, there is provided the use of the anti-BDCA2 antibody or antigen-binding fragment thereof of the present disclosure, or the pharmaceutical composition of the present disclosure, in the manufacture of a medicament for treating a disease.

[0330] In particular embodiments, the disease or disorder is an inflammatory disease or an autoimmune disease.

[0331] In particular embodiments, the inflammatory or autoimmune disease is selected from systemic lupus erythematosus, discoid lupus, lupus nephritis, cutaneous lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, systemic sclerosis, progressive systemic sclerosis (scleroderma), psoriasis, psoriatic arthritis, type I diabetes, fibrosis (e.g., skin fibrosis, lung fibrosis), pemphigus vulgaris, Graves’ disease, scleroderma (localized scleroderma), Sjogren’s disease, Hashimoto’s disease, dermatomyositis, polymyositis, asthma, Behcet’s disease, Crohn’s disease, autoimmune glomerulonephritis, membranous glomerulopathy, juvenile rheumatoid arthritis, mixed connective tissue disease, multiple sclerosis, nephrotic syndrome, panniculitis, pemphigoid, pemphigus, pemphigus erythematosus, pemphigus foliaceus, pemphigus vulgaris, polymyalgia rheumatica, Raynaud’s phenomenon / syndrome, Sjogren’s syndrome, and ulcerative colitis.

[0332] In particular embodiments, the inflammatory or autoimmune disease is selected from systemic lupus erythematosus, discoid lupus, lupus nephritis, cutaneous lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, systemic sclerosis (scleroderma), psoriasis, type I diabetes, fibrosis (e.g., skin fibrosis), pemphigus vulgaris, Graves’ disease, scleroderma, Sjogren’s disease, and Hashimoto’s disease, dermatomyositis, and polymyositis.

[0333] In particular embodiments, the inflammatory or autoimmune disease is systemic lupus erythematosus.

[0334] In particular embodiments, the inflammatory or autoimmune disease is discoid lupus.

[0335] In particular embodiments, the inflammatory or autoimmune disease is cutaneous lupus erythematosus.

[0336] In particular embodiments, the disease or condition is a BDCA2-mediated disease.

[0337] In a ninth aspect, the disclosure provides a method of inducing death of plasmacytoid dendritic cells in a subject, the method comprising contacting a plasmacytoid dendritic cell expressing BDCA2 with an amount of an anti-BDCA2 antibody or antigen-binding fragment thereof of the disclosure, or a pharmaceutical composition of the disclosure.

[0338] In a tenth aspect, the disclosure provides a method of reducing the production of inflammatory cytokines or chemokines by plasmacytoid dendritic cells in a subject, the method comprising contacting plasmacytoid dendritic cells expressing BDCA2 with an amount of an anti-BDCA2 antibody or antigen-binding fragment thereof of the disclosure, or a pharmaceutical composition of the disclosure. In particular embodiments, the inflammatory cytokines or chemokines are selected from the group consisting of type I interferons, IL-6, TNF-a, CCL3, CCL4, IP10, and RANTES.

[0339] In an eleventh aspect, there is provided use of an anti-BDCA2 antibody or antigen-binding fragment thereof of the disclosure, or a pharmaceutical composition of the disclosure, in the manufacture of a medicament for inducing plasmacytoid dendritic cell death.

[0340] In a twelfth aspect, there is provided use of an anti-BDCA2 antibody or antigen-binding fragment thereof of the disclosure, or a pharmaceutical composition of the disclosure, in the manufacture of a medicament for reducing the production of inflammatory cytokines or chemokines by plasmacytoid dendritic cells.

[0341] In a thirteenth aspect, an anti-BDCA2 antibody or antigen-binding fragment thereof of the disclosure, or a pharmaceutical composition of the disclosure, is useful as a medicament for inducing plasmacytoid dendritic cell death, or for reducing the production of inflammatory cytokines or chemokines by plasmacytoid dendritic cells. BRIEF DESCRIPTION OF DRAWINGS

[0342] Figures 1A and IB show the inhibitory effect of humanized antibodies on TLR9-induced IFN-a secretion. Figure 1A is the inhibition of IFN-a secretion by healthy human PBMCs; Figure IB is the inhibition of IFN-a secretion by SLE patient PBMCs.

[0343] Figure 2 shows the inhibitory effect of Fc mutant antibodies on TLR9-induced IFN-a secretion.

[0344] Figure 3 shows the killing activity of anti-BDCA2 antibodies mediated by ADCC action on target cells.

[0345] Figure 4 shows the endocytosis activity of anti-BDCA2 antibodies of the disclosure. DETAILED DESCRIPTION

[0346] The present disclosure will be further described by the following non-limiting examples, as will be apparent to those skilled in the art. Numerous modifications can be made to the present disclosure without departing from the spirit of the present disclosure, and it is intended to include all such modifications as fall within the scope of the present disclosure. The following examples are intended for illustration only and should not be construed as limiting the scope of the present disclosure, as the embodiments necessarily are numerous and diverse. The use of any and all examples, or exemplary language (e.g., "such as" and "preferably"), is intended to merely enrich the description of the specific embodiments and is not intended to limit the scope of the disclosure. The terms used in the specification are for the purpose of describing particular embodiments only and are not intended to be limiting, as the scope of the present disclosure is defined in the appended claims.

[0347] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are described. Unless otherwise specified, the experimental methods described below are conventional methods or are described in product specifications. The experimental materials used are readily available from commercial sources unless otherwise stated. All publications mentioned in the specification are herein incorporated by reference to disclose and describe the methods and / or materials in connection with which the publications are cited.

[0348] The terms

[0349] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0350] Unless the context clearly requires otherwise, throughout the description and the claims, the words "comprise," "comprising," "include," "including," and the like are to be construed in an inclusive sense, as opposed to an exclusive or exhaustive sense. That is, unless otherwise noted, the description, including the following claims, use "comprise" and "comprising" in the inclusive sense of "including but not limited to."

[0351] The term "and / or", when used between two or more options, is to be construed as meaning any one of the options or any combination of two or more of the options.

[0352] The term "BDCA2" refers to blood dendritic cell antigen 2 (BDCA2), in any recombinant or naturally occurring form, variants or homologs thereof that maintain the activity of BDCA2, for example at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% of the activity. The variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the entire sequence or a partial sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) of a naturally occurring BDCA2 protein.

[0353] Unless otherwise indicated, the term "BDCA2" includes unprocessed full-length BDCA2 as well as any form of BDCA2 that results from processing in a cell. The term encompasses "full-length" unprocessed BDCA2 as well as any form of BDCA2 or any fragment thereof, such as a splice variant or allelic variant, that results from intracellular processing. In one embodiment, BDCA2 refers to full-length or a fragment thereof from human or cynomolgus BDCA2, such as a mature fragment thereof that lacks the signal peptide.

[0354] The term "antibody" is used in the broadest sense, and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, full-length antibodies, as long as they exhibit the desired antigen-binding activity. Typically, a natural IgG antibody is a heterotetrameric protein composed of two light chains and two heavy chains that are linked via disulfide bonds. From N- to C-terminus, each heavy chain has one variable region (VH), three constant domains (CH1, CH2, and CH3). From N- to C-terminus, each light chain has one variable region (VL), one constant light domain (CL). Depending on the context, the skilled artisan can determine the specific meaning of "antibody."

[0355] The "class" of an antibody refers to the type of constant domain or constant region possessed by its heavy chain. Antibodies are classified into five major classes: IgA, IgD, IgE, IgG, and IgM, and several of these can be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called a, d, e, g, and m, respectively.

[0356] The term "anti-BDCA2 antibody" refers to an antibody molecule that specifically binds to BDCA2 and is capable of inhibiting BDCA2 activity. An anti-BDCA2 antibody is capable of inhibiting BDCA2 activity, for example, by at least partially or completely blocking stimulation of BDCA2, reducing, preventing or delaying activation of BDCA2, or inactivating, desensitizing or down-regulating signal transduction, activity or amount of BDCA2, relative to the absence of the anti-BDCA2 antibody. In some embodiments, the antibody can inhibit BDCA2 activity by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or more, relative to a control.

[0357] An "antibody fragment" or "antigen binding fragment" is a molecule other than an intact antibody that comprises a portion of an intact antibody that retains the antigen binding ability of the intact antibody. Examples of antibody fragments include but are not limited to Fv, Fab, Fab', Fab'-SH, F(ab')2, single-domain antibody, single-chain Fab (scFab), diabodies, linear antibodies, single-chain antibodies (e.g., scFv); and multispecific antibodies formed from antibody fragments.

[0358] A "Fab" is composed of one light chain and the CH1 and variable region of one heavy chain.

[0359] A "Fab' fragment" is a Fab fragment with one or more cysteine residues at the C-terminus of the CH1 domain.

[0360] A "F(ab')2 fragment" is a bivalent fragment comprising two Fab' fragments linked by disulfide bridge at the hinge region.

[0361] "Fab'-SH" refers to an Fab' in which the cysteine residue(s) of the constant regions bear an available thiol group.

[0362] A "single-chain Fab fragment" is a polypeptide consisting of an antibody heavy chain variable domain (VH), an antibody constant domain 1 (CH1), an antibody light chain variable domain (VL), an antibody light chain constant domain (CL) and a linker, wherein said antibody domains and said linker have one of the following orders from N- to C-terminal direction: a) VH-CH1-linker-VL-CL, b) VL-CL-linker-VH-CH1, c) VH-CL-linker-VL-CH1 or d) VL-CH1-linker-VH-CL; and wherein said linker is a peptide linker. In some embodiments, the peptide linker is a polypeptide of at least 30 amino acids, preferably a polypeptide of 32-50 amino acids.

[0363] A "diabody" has two antigen binding sites, comprising a heavy chain variable domain (VH) and a light chain variable domain (VL) connected to one another in the same polypeptide chain.

[0364] “Linear antibody” comprising a pair of tandem Fd segments (VH-CH1-VH-CH1) which, together with complementary light chain polypeptides, form a pair of antigen binding regions.

[0365] “Fv fragment” has the VL and VH domains of one arm of an antibody.

[0366] “Single-domain antibody” is an antibody fragment which comprises all or a portion of the heavy chain variable domain or all or a portion of the light chain variable domain of an antibody.

[0367] Single chain antibody (single chain antibody fragment, scFv) is an antibody formed by connecting the heavy chain variable region and the light chain variable region by a linker.

[0368] “Fc” contains two heavy chain fragments comprising CH2 and CH3 domains. Two heavy chain fragments are held together by disulfide bonds and by hydrophobic interactions of CH3 domains. As a supplement, in the anti-BDCA2 antibody or antigen-binding fragment thereof of the present application, although the C-terminus of the Fc region is the complete C-terminus ending with PGK, it can also be a truncated C-terminus. Exemplarily, one or two C-terminal residues are removed in the truncated C-terminus (e.g., truncated C-terminus ending with PG). In the composition comprising the antibody, both the antibody with the complete C-terminus and the antibody with the truncated C-terminus can be included.

[0369] The term “variable region” or “variable domain” refers to the domain of the antibody heavy or light chain that is involved in binding the antibody to an antigen. The variable domains of the heavy and light chains of natural antibodies generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three complementary determining regions (CDRs) (see, e.g., Kindt et al. Kuby Immunology, 6th ed., W.H. Freeman and Co. p. 91 (2007)). A single VHor VLdomain is sufficient to confer antigen-binding specificity.

[0370] A "complementarity determining region" or "CDR region" or "CDR" is a region in an antibody variable domain that is hypervariable in sequence and forms structurally defined loops ("hypervariable loops") and / or contains antigen contact residues ("antigen contacts"). CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs in a variable domain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially from the N-terminus. The precise amino acid sequence boundaries of each CDR in a given variable region amino acid sequence can be determined using any of a number of well-known antibody CDR assignment systems, or combinations thereof, including, for example: Chothia based on the three-dimensional structure of the antibody and the topology of the CDR loops (Chothia et al. (1989) Nature 342: 877-883, Al-Lazikani et al., "Standard conformations for the canonical structures of immunoglobulins", Journal of Molecular Biology, 273, 927-948 (1997)), Kabat based on antibody sequence variability (Kabat et al., Sequences of Proteins of Immunological Interest, 4th Ed., U.S. Department of Health and Human Services, National Institutes of Health (1987)), AbM (University of Bath), Contact (University College London), the international ImMunoGeneTics database (IMGT) (http: / / imgt.cines.fr / ), and North CDR definitions based on affinity propagation clustering with a large number of crystal structures. Correspondence between the various numbering systems is well understood by those skilled in the art. In other words, when a CDR sequence under one numbering system and its position in an antibody are provided, the skilled person is able to determine the corresponding CDR sequence under another numbering system and its position in the antibody. The different numbering systems are considered as equivalent technical solutions.

[0371] In one embodiment, the CDRs of the antibodies of the disclosure are determined positions according to the Kabat numbering scheme.

[0372] The anti-BDCA2 antibodies of the present disclosure can also comprise antibodies having "alternative CDRs." "Alternative" CDRs refer to CDRs (CDR1, CDR2, and CDR3) defined according to any of Chothia (from AbYsis), AbM CDRs, or ImMunoGeneTics database (IMGT). These alternative CDRs can be obtained, for example, by using the AbYsis database (www.bioinf.org.uk / abysis / sequence_input / key_annotation / key_annotation.cg). Exemplary, the amino acid sequences of the "alternative" CDR1, 2, and 3 of the heavy chain variable region and light chain variable region of 10C9 VH5VL6 are compared to the CDRs defined according to Kabat in the following table.

[0373] Unless otherwise indicated, in the present disclosure, when referring to residue positions in antibody variable regions and CDRs, including heavy chain variable region residues, the numbering position refers to the numbering according to the Kabat numbering system.

[0374] A "chimeric antibody" is an antibody that fuses the variable region of an antibody of one species (e.g., murine origin) to the constant region of an antibody of another species (e.g., human).

[0375] A "humanized antibody" refers to a chimeric antibody that contains amino acid residues from a non-human CDR and amino acid residues from a human FR. In some embodiments, all or substantially all of the CDRs (e.g., CDRs) in a humanized antibody correspond to those of a non-human antibody, and all or substantially all of the FRs correspond to those of a human antibody. A humanized antibody optionally can contain at least a portion of an antibody constant region derived from a human antibody. A "humanized form" of an antibody (e.g., a non-human antibody) refers to an antibody that has been humanized.

[0376] The terms "binds" or "binds specifically" as used herein means that the binding is selective for the antigen and can be distinguished from unwanted or non-specific interactions. The ability of an antigen binding site to bind to a particular antigen can be determined by enzyme-linked immunosorbent assay (ELISA) or conventional binding assays known in the art, such as by radioimmunoassay (RIA) or biolayer interferometry assay or MSD assay or surface plasmon resonance (SPR).

[0377] The term "half maximal effective concentration (EC 50 " is the concentration of a drug, antibody, or toxic agent that induces a response that is 50% between the baseline and maximum after a specified exposure time.

[0378] As used herein, the term "percent (%) amino acid sequence identity" or simply "identity" is defined as the percentage of amino acid residues in the candidate amino acid sequence that are identical with the same amino acid residues in the reference amino acid sequence, after aligning the sequences (and introducing gaps, if necessary) to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Sequence alignment for purposes of determining percent amino acid sequence identity can be achieved using various methods, for example, using publically available computer software such as BLAST, BLAST-2, ALIGN, or the MEGALIGN DNA STAR software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.

[0379] As an example, "the heavy chain variable region comprises an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 58" means that the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, HCDR3 set forth in SEQ ID NO: 16, and the regions outside of the CDRs allow introduction of amino acid mutations such that the heavy chain variable region has at least 85% sequence identity to SEQ ID NO: 58.

[0380] "Amino acid mutations" include amino acid substitutions, deletions, insertions, modifications, or any combination thereof. Any combination of substitutions, deletions, insertions and modifications can be made to arrive at the final construct, so long as the final construct possesses the desired properties, such as amino acid substitutions that reduce Fc region homodimerization. Amino acid substitutions can be introduced into an antibody of interest, and the products screened for a desired activity, such as retained / improved antigen binding, decreased immunogenicity. Amino acid sequence deletions and insertions include deletions and insertions at the amino- and / or carboxy-terminus of a polypeptide chain. In one embodiment, the amino acid mutation is a non-conservative amino acid substitution, i.e., the replacement of one amino acid by another amino acid with different structural and / or chemical properties. Amino acid mutations can be generated using genetic or chemical methods known in the art. Genetic methods can include site-directed mutagenesis, PCR, gene synthesis, and the like.

[0381] In the present disclosure, various ways can be used to indicate the same amino acid mutation. Exemplarily, the amino acid residue at a particular position can be represented in the way of position + amino acid residue, such as 252Y, 254T, which means the amino acid residue at position 252 is Y, and the amino acid residue at position 254 is T. The amino acid positions are obtained according to the EU numbering.

[0382] "Nucleic acid" is used interchangeably with "polynucleotide" and refers to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double-stranded form. The nucleic acid is synthetic, naturally occurring, and non-naturally occurring. Unless otherwise indicated, nucleic acid sequences also encompass conservative variants (e.g., degenerate substitutions) and complements thereof, as well as the explicitly indicated sequences.

[0383] "Vector" means a polynucleotide molecule that is capable of transporting another polynucleotide to which it has been linked. One type of vector is a "plasmid," which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, such as an adeno-associated viral vector (AAV), into which additional DNA segments are ligated. Some vectors are capable of autonomous replication in a host cell, while others can be integrated into the host genome and replicated with the host genome.

[0384] "Host cell," "cell line" are used interchangeably and refer to a cell into which exogenous nucleic acid has been introduced and its progeny, without regard to the number of passages. Progeny can not be completely identical to the parental cell in nucleic acid content, for example, mutations that occur during replication, but are still within the scope of the term "host cell" as used herein. Exemplary host cells include, but are not limited to, CHO, NSO, COS, SP2 cells, HeLa cells, BHK cells, human hepatocellular carcinoma cells, A549 cells, 3T3 cells, and HEK-293 cells. Fungal cells include yeasts, such as, but not limited to, Pichia, Saccharomyces, Hansenula, Kluyveromyces.

[0385] The term "BDCA2-mediated disease" refers to a disease in which BDCA2 is involved in the onset, progression, or persistence, e.g., involves activation (e.g., abnormal activation or over-activation) of BDCA2, and the involvement of BDCA2 directly or indirectly results in at least one of the following effects: initiation / occurrence of the disease; increase / deepening of pathological changes of the disease; expansion of the site / extent of the disease impact; aggravation of the body damage caused by the disease; increase of the pain caused by the disease; insensitivity / resistance of the disease to therapeutic measures; decrease of the self-healing tendency of the disease; and poor prognosis of the disease. In some embodiments of the present disclosure, the BDCA2-mediated disease is an inflammatory disease or an autoimmune disease; in some specific embodiments of the present disclosure, the BDCA2-mediated disease is systemic lupus erythematosus, discoid lupus, lupus nephritis, cutaneous lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, systemic sclerosis (scleroderma), psoriasis, type I diabetes, fibrosis (e.g., skin fibrosis), pemphigus vulgaris, psoriasis, Graves' disease, scleroderma, Sjogren's disease, Hashimoto's disease, dermatomyositis, and polymyositis.

[0386] A "subject" or "individual" refers to an animal, preferably a mammal. According to particular embodiments, the subject is a mammal, including, for example, a camel, a horse, a cow, a pig, a sheep, a cat, a dog, a rabbit, a rat, a guinea pig, a mouse, a primate (e.g., a human). In particular embodiments, the subject is a human.

[0387] The term "treatment" refers to slowing, interrupting, arresting, stopping, reducing, or reversing the progression or severity of an existing symptom, disorder, condition, or disease. Desirable effects of treatment include, but are not limited to, preventing occurrence or reoccurrence of the disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis. In some embodiments, the antibodies of the disclosure are used to delay development of a disease or to slow the progression of a disease.

[0388] The term "prevention" includes inhibition of the occurrence or development of a disease or disorder or symptoms of a particular disease or disorder.

[0389] The term "therapeutically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic result. A therapeutically effective amount of an antibody or antibody fragment or composition thereof can vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the antibody or antibody moiety to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the antibody or antibody fragment or composition are outweighed by the therapeutically beneficial effects.

[0390] The term "prophylactically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Generally, the prophylactically effective amount will be less than the therapeutically effective amount since the prophylactic dose is used before or at an earlier stage of disease than the therapeutic dose.

[0391] The term "pharmaceutical composition" refers to a composition that is in a form suitable for administration into a subject and that includes an active ingredient in an amount effective to achieve its intended biologic activity, and that does not include additional ingredients that are unacceptable with respect to toxicity to the subject to which the composition is administered.

[0392] A pharmaceutical composition as described herein can include a pharmaceutically acceptable carrier, diluent, buffer, or excipient. As used herein, a "pharmaceutically acceptable carrier, diluent, buffer, or excipient" includes any and all solvents, media, coatings, isotonic, stabilizing, and anti-oxidizing agents, and the like.

[0393] The formulation of drugs is a well-known technology, further described, for example, in Gennaro (ed.), Remington: The Science and Practice of Pharmacy, 20th ed., Lippincott, Williams & Wilkins (2000); Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th Ed., Lippincott Williams & Wilkins Publishers (1999).

[0394] The pharmaceutical composition can also be in a variety of forms, including, for example, liquid, semi-solid, and solid dosage forms. For example, liquid solutions (e.g., injectable and infusible solutions), suspensions, tablets, pills, powders, liposomes, suppositories. The preferred form can depend on the mode of administration and therapeutic application. Typically, the pharmaceutical composition described herein is in the form of an injectable or infusible solution.

[0395] In one embodiment, the anti-BDCA2 antibody or antigen-binding fragment thereof according to herein is provided at a suitable concentration in a buffer and stored at 2-8°C.

[0396] The pharmaceutical composition can be administered parenterally, e.g., intravenous, subcutaneous, intraperitoneal, or intramuscular injection. As used herein, "parenteral administration" includes, but is not limited to, injection and infusion, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural, and intrasternal. In some specific embodiments, the antibody or antigen-binding fragment thereof that specifically binds to human BDCA2 is administered intravenously.

[0397] In some embodiments, the anti-BDCA2 antibody or antigen-binding fragment thereof can be prepared with controlled release carriers (e.g., controlled release formulations, implants, microencapsulated delivery systems). Methods for preparing such formulations are generally known.

[0398] The following are examples of the practice of the present disclosure and should not be construed as limiting the scope of the present disclosure in any way.

[0399] Example 1 Preparation of murine anti-BDCA2 antibody

[0400] BDCA2 ECD-hFc Tag protein was expressed by BDBiosciences, with an expression level of 10.3 mg / L, and a purity of >95% by SDS-PAGE.

[0401] The amino acid sequence of human BDCA2 ECD-hFc Tag is as follows:

[0402] After immunizing Balb / c mice (6-8 weeks old) with human BDCA2 ECD-Fc Tag protein at a dose of 100 μg per mouse, the mice were re-immunized at a dose of 50 μg per mouse on day 14, day 28 and day 42, and one week after the fourth immunization, the antibody titers in the serum collected from the tail vein of each mouse were determined by ELISA. The mice with sufficient titers were boosted with 50 μg of protein, and the mice were sacrificed 3 days later to collect spleen cells. The spleen cells were fused with myeloma cells SP2 / 0 (purchased from Shanghai Cell Bank) using PEG (Sigma; Catalog No. P7306) according to the conventional method. After 10 days of culture, the supernatant of the hybridoma cells was detected for binding activity to human BDCA2 protein by ELISA, and the positive hybridoma cells were selected and frozen.

[0403] The antibody titration in mouse serum and the detection method of hybridoma supernatant are as follows:

[0404] Human BDCA2 protein (Acro; Catalog No. CLC-H5245) was diluted to a concentration of 0.25 μg / mL in PBS to coat a 96-well plate at 4°C overnight. The plate was blocked with 5% BSA-PBST blocking solution at 37°C for 1 hour, and after PBST washing, 50 μL of serum dilution or hybridoma cell supernatant from immunized mice was added and incubated at 37°C for 1 hour. After washing the plate, HRP-labeled goat anti-mouse IgG (Sigma, Catalog No. A2554, diluted 1:5000) was added for detection. After washing the plate, TMB was used for color development, and the plate was measured at 450 nm using an enzyme-labeled instrument (TECAN SPARK).

[0405] The results showed that the serum of human BDCA2 ECD-Fc immunized mice could specifically bind to the immunogen, and the titer of the mouse serum was more than 1:256,000; the positive hybridoma cells were screened and frozen.

[0406] Example 2 Sequencing of the variable region of murine hybridoma and expression of human-murine chimeric antibody

[0407] The positive hybridoma cells obtained in Example 1 were subjected to RNA extraction and reverse transcription to cDNA according to the conventional method, and after sequencing, the heavy chain variable region and light chain variable region sequences of the positive clones were obtained. Further, the amino acid sequences were analyzed, and the CDR amino acid sequences were determined based on the database of Kabat (Kabat, E. A. et al. 1991).

[0408] To express the chimeric antibody, the nucleic acid sequences of the heavy chain and light chain variable regions obtained by sequencing were respectively connected with the human antibody heavy chain IgG1 constant region and the human antibody light chain kappa constant region, cloned into the vector pcDNA3.4 and transfected into CHO-K1 cells (purchased from Baiying Biology). After 3 days of culture, the supernatant was purified with protein A, and the antibody was detected and analyzed for protein concentration and purity. The results showed that the purity of the chimeric antibody obtained by the disclosure was >95%. The CDR sequences of the mouse-derived antibody obtained by the disclosure are shown in Table 1.

[0409] Table 1 CDR sequences of mouse-derived antibodies

[0410] The variable regions of the mouse-derived antibodies are as follows:

[0411] Human IgG1 constant region:

[0412] Human light chain kappa constant region:

[0413] Note: In the above sequences, the underlined part is the CDR region.

[0414] Example 3 Humanization of antibodies

[0415] The chimeric antibodies ch-20A2, ch-6H1 and ch-10C9 were humanized by the method of complementarity determining region (CDR) grafting. The nucleic acid sequences of the heavy chain and light chain variable regions of the chimeric antibodies were compared with the human IgG gene sequence database to identify the best matching human germline IgG gene sequence, and then the CDR regions of the heavy chain and light chain of the chimeric antibodies were respectively grafted into the framework sequence of the matching human IgG heavy chain variable region gene and light chain variable region gene, followed by individual amino acid back mutation and PTM (Post-translational modification) removal to obtain humanized antibodies.

[0416] The obtained humanized antibody variable region sequences are as follows, wherein the underlined part represents the corresponding CDR region:

[0417] The 20A2 humanized antibody has mutations in HCDR2, LCDR1 and LCDR2 as compared with the CDR sequences of the corresponding murine antibody. The 6H1 humanized antibody has mutations in LCDR1 and LCDR2. The 10C9 humanized antibody has mutations in HCDR2 and LCDR1. Specifically, the CDR sequences of the humanized antibodies with mutations are shown in Table 2 below, and the italicized bold parts represent the mutated amino acids as compared with the murine sequences.

[0418] Table 2 CDR region sequences of humanized antibodies

[0419] The nucleic acid sequences of the heavy chain and light chain variable regions of the humanized antibodies were respectively ligated and cloned into the nucleic acid sequences of the heavy chain IgGl constant region of the human antibody and the light chain kappa constant region of the human antibody according to the method of Example 2, and the humanized antibodies were obtained by transient expression in an expression vector pcDNA3.4.

[0420] Table 3-1 Variable region sequence combinations of 20A2 humanized antibody

[0421] Table 3-2 Variable region sequence combinations of 6H1 humanized antibody

[0422] Table 3-3 Variable region sequence combinations of 10C9 humanized antibody

[0423] The sequence of the exemplary humanized antibody 20A2-VH6VL11 is as follows:

[0424] The heavy chain sequence of 20A2-VH6VL11 is as follows:

[0425] The light chain sequence of 20A2-VH6VL11 is as follows:

[0426] The underlined part is the variable region sequence.

[0427] The sequence of the exemplary humanized antibody 6H1-VH1VL2 is as follows:

[0428] The heavy chain sequence of 6H1-VH1VL2 is as follows:

[0429] The light chain sequence of 6H1-VH1VL2 is as follows:

[0430] The underlined part is the variable region sequence.

[0431] The sequence of the exemplary humanized antibody 10C9-VH6VL5 is as follows:

[0432] 10C9-VH6VL5 heavy chain sequence:

[0433] 10C9-VH6VL5 light chain sequence:

[0434] wherein the underlined portion is the variable region sequence.

[0435] Fc mutations of humanized antibodies of Example 4

[0436] The heavy chain constant region of the humanized antibodies screened in Example 3 was introduced with M252Y, S254T and T256E (YTE) mutations, or with M428L and N434S (LS) mutations to increase the affinity of the antibodies to FcRn.

[0437] The sequences of exemplary mutant antibodies are as follows:

[0438] 10C9-VH6VL5(YTE) heavy chain sequence:

[0439] wherein the underlined portion is the heavy chain variable region sequence.

[0440] 10C9-VH6VL5(YTE) light chain sequence:

[0441] wherein the underlined portion is the light chain variable region sequence.

[0442] 10C9-VH6VL5(LS) heavy chain sequence:

[0443] wherein the underlined portion is the heavy chain variable region sequence.

[0444] 10C9-VH6VL5(LS) light chain sequence:

[0445] wherein the underlined portion is the light chain variable region sequence.

[0446] 20A2VH6VL11(YTE) heavy chain sequence:

[0447] 20A2VH6VL11(YTE) light chain sequence:

[0448] 20A2VH6VL11(LS) heavy chain sequence:

[0449] 20A2 VH 6 VL11 (LS) light chain sequence:

[0450] 6H1-VH1 VL2 (YTE) heavy chain sequence:

[0451] 6H1-VH1 VL2 (LS) light chain sequence:

[0452] 6H1-VH1 VL2 (LS) heavy chain sequence:

[0453] 6H1-VH1 VL2 (LS) light chain sequence:

[0454] In addition, 24F4 and 3E5 are used as controls in the present disclosure, wherein 24F4 is produced according to the sequence disclosed in patent WO2014093396, the light and heavy chains correspond to SEQ ID NO: 3 and SEQ ID NO: 4 in the patent, respectively; 3E5 is produced according to the sequence disclosed in patent WO2021023793, the light and heavy chains correspond to SEQ ID NO: 21 and SEQ ID NO: 25 in the patent, respectively.

[0455] Example 5 Detection of antibody activity

[0456] 5.1 Detection of antibody affinity

[0457] Octet R8 (purchased from Sartorius) was used to detect the affinity of the antibody to BDCA2 protein. Human BDCA2 protein (hBDCA2, ACRO; Catalog No: CLC-H5245) or monkey BDCA2 protein (cynoBDCA2, Kactus; Catalog No: BCA-CM102) was diluted to 5 pg / mL, and then 2-fold gradient dilution was used as the analyte. The antibody to be tested was used as the ligand, the ligand solidification height was 1.0 nm, the ligand and analyte binding time was 45 seconds, and the analyte dissociation time was 200 seconds. After the experiment, kinetic fitting model was used for analysis by Octet Analysis Studio 12.2, and the results are shown in Tables 4 and 5.

[0458] Table 4 Affinity constant of chimeric antibody to hBDCA2 protein

[0459] The results in Table 4 show that the chimeric antibodies ch-20A2, ch-6H1 and ch-10C9 can all specifically bind to human BDCA2 protein.

[0460] Table 5 Affinity constants of humanized antibodies to hBDCA2 protein and cyno BDCA2 protein

[0461] Table 5 shows that the humanized antibodies have comparable affinity to the chimeric antibody, and the antibodies of the disclosure can specifically bind to BDCA2 of human and cynomolgus monkey.

[0462] 5.2 Detection of affinity of antibodies to Fc receptor

[0463] The binding activity of 10C9-VH6VL5(YTE) and 10C9-VH6VL5(LS) to FcRn was detected using Octet R8 instrument (Sartorius). The antibody to be tested was diluted to 20 μg / mL, and after 2-fold dilution, it was used as the analyte. The ligand was 2 μg / mL biotin-labeled FcRn (ACRO; Catalog No: FCM-H82W4), the ligand immobilization height was 0.5 nm, the ligand and analyte binding time was 60 seconds, and the analyte dissociation time was 60 seconds. After the end of the experiment, the results were analyzed using the kinetic fitting model in Octet Analysis Studio 12.2, and the results are shown in Table 6.

[0464] Table 6 Affinity constants of Fc mutant antibodies to FcRn

[0465] Table 6 shows that the Fc mutant antibodies 10C9-VH6VL5(YTE) and 10C9-VH6VL5(LS) have improved affinity to FcRn compared to 10C9-VH6VL5.

[0466] 5.3 Detection of binding of antibodies to BDCA2 protein by ELISA

[0467] hBDCA2 protein (Kactus; Catalog No: BCA-HM102) or cyno BDCA2 protein (Kactus; Catalog No: BCA-CM102) was diluted with PBS to 1 μg / mL, and a 96-well plate was coated and incubated at 4°C overnight. The plate was blocked with 5% BSA-PBS blocking solution at 37°C for 1 hour, washed with PBST, and the antibody to be tested was diluted to 20 μg / mL, and after 6-fold gradient dilution, it was added to the plate and incubated at 37°C for 1 hour. After washing the plate, HRP-labeled goat anti-human IgG (Sigma; Catalog No: A0170) secondary antibody was added and incubated at room temperature for 1 hour. After color development with TMB, the reaction was terminated, and the plate was placed in a microplate reader (TECAN SPARK) to measure at 450 nm. The results are shown in Tables 7-1 to 7-4.

[0468] Results show that chimeric antibodies ch-20A2, ch-6H1 and ch-10C9 have good binding activity to both human BDCA2 and monkey BDCA2; the binding activity of humanized antibodies 20A2, 6H1 and 10C9 to BDCA2 protein is comparable to that of chimeric antibodies.

[0469] Table 7-1 Binding activity of chimeric antibodies to BDCA2

[0470] Table 7-2 Binding activity of humanized antibodies to hBDCA2

[0471] Table 7-3 Binding activity of humanized antibodies to hBDCA2

[0472] Table 7-4 Binding activity of humanized antibodies to hBDCA2

[0473] 5.4 Detection of the ability of antibodies to inhibit TLR9-induced IFN-α

[0474] The ability of antibodies to inhibit TLR9 agonist (CpG-A)-induced IFN-α was detected using PBMCs from healthy people and SLE patients. The PBMC cells were resuscitated, resuspended with complete culture medium (RPMI1640+10%FBS+1xNEAA+1xSodium Pyruvate+1xGlutaMax), inoculated into 96-well cell culture plates at 0.5-1x10 6 cells per well; gradient-diluted test antibodies (10μg / mL for the first well, 20-fold dilution for 2 concentration points, 10-fold dilution for 1 concentration point, and then 3-fold dilution for 4 concentration points) and ODN2216 (Invivogen; Catalog No: tlrl-2216-1) with a final concentration of 0.5μM were added, and incubated at 37°C overnight (18 hours). The supernatant was collected, and the IFN-α concentration in the supernatant was detected using an IFN-α ELISA kit (Duo; Catalog No: 1110013). The results are shown in Tables 8-1, 8-2, 9 and Figures 1A, 1B and 2.

[0475] Results show that humanized antibody 10C9-VH6VL5 has a significant inhibitory effect on TLR9-induced IFN-α secretion, and the activity is better than that of 3E5 and 24F4; the humanized antibody also has a strong inhibitory ability on TLR9-induced IFN-α secretion by PBMCs from SLE patients. In addition, Fc mutant antibodies YTE and LS have comparable activity to 10C9-VH6VL5 in TLR9-induced IFN-α secretion.

[0476] Table 8-1 Inhibition of IFN-alpha secretion by antibodies from PBMC of healthy humans

[0477] Table 8-2 Inhibition of IFN-alpha secretion by antibodies from PBMC of SLE patients

[0478] Table 9 Inhibition of IFN-alpha secretion by Fc mutant antibodies from PBMC of healthy humans

[0479] 5.5 Detection of the ability of antibodies to inhibit TLR7-induced IFN-alpha

[0480] The inhibition of IFN-alpha production by humanized antibodies on PBMC stimulated by TLR7 agonist (R837) was detected using the following method. Human PBMC cells were recovered, resuspended with complete medium (RPMI 1640 + 10% FBS + 1x NEAA + 1x Sodium Pyruvate + 1x GlutaMax), seeded at 5x10 5 cells per well in 96-well cell culture plates; different concentrations of the antibody to be tested were added: 10 pg / mL for the first well, 2 concentration points with 20-fold dilution, 1 concentration point with 10-fold dilution, and 4 concentration points with 3-fold dilution; the cells were stimulated with R837 (Invivogen; Cat. No: tlrl-imqs) at a concentration of 1 pg / mL and incubated at 37°C overnight (18 hours). The supernatant was collected and the concentration of IFN-alpha in the supernatant was detected using an IFN-alpha ELISA kit (DuoSet; Cat. No: 1110013). The results are shown in Table 10.

[0481] The results show that humanized antibody 10C9-VH6VL5 has a significant inhibitory effect on R837-induced IFN-alpha secretion.

[0482] Table 10 Inhibition of TLR7-induced IFN-alpha by humanized antibodies

[0483] 5.6 Detection of the ability of antibodies to inhibit immune complex-induced IFN-alpha

[0484] The ability of humanized antibodies to inhibit the release of IFN-alpha from human PBMC cells stimulated by immune complexes (IC) was detected. Human PBMC cells were recovered, resuspended with complete medium (RPMI 1640 + 10% FBS + 1x NEAA + 1x Sodium Pyruvate + 1x GlutaMax), seeded at 8x10 5Cells were seeded into 96-well cell culture plates; different concentrations of the antibody to be tested were added: the first well was treated with a concentration of 0.5 μg / mL, 20-fold dilution for one concentration point, 3-fold dilution for three concentration points, and 5-fold dilution for three concentration points; 2 μL of human anti-RNP auto-antigen (Raybiotech; Catalog No. MD-14-0513) and 1 μL of RNP-Sm (AROTEC, Catalog No. ATR01-10) were taken, respectively, and incubated at room temperature for 30 minutes, and then added to the 96-well cell culture plates, which were incubated at 37°C overnight (18 hours). The supernatant was collected, and the IFN-α concentration in the supernatant was detected using an IFN-α ELISA kit (Duo, Catalog No. 1110013). The results are shown in Tables 11 and 12.

[0485] The results in Table 11 show that the humanized antibodies have a significant inhibitory effect on IC-stimulated IFN-α secretion. The results in Table 12 show that the Fc mutant antibodies YTE and LS have an activity comparable to that of 10C9-VH6VL5 in terms of IFN-α secretion induced by immune complexes.

[0486] Table 11 Inhibitory effect of humanized antibodies on immune complex-induced IFN-α

[0487] Table 12 Inhibitory effect of Fc mutant antibodies on immune complex-induced IFN-α

[0488] Example 6 Detection of ADCC activity of humanized antibodies

[0489] After cloning the human BDCA2 full-length cDNA sequence (NM_130441.3) and human FcεRIγ (NM_004106.1), HEK293 cells were transfected, and after pressure screening, a cell strain HEK293-hBDCA2 overexpressing human BDCA2 was obtained.

[0490] PBMC cells were used to detect the ADCC activity of the humanized antibodies. The PBMC cells were recovered, and the cell density was adjusted to 5 x 10 6 HEK-hBDCA2 cells were collected, and the cell density was adjusted to 2.5 x 10 5 The antibodies were diluted to 0.9 μg / mL, and then 7-fold gradient dilution was performed, and 40 μL / well was added to the plates, which were incubated at 37°C for 6 hours; an LDH kit (Roche; Catalog No. 04744934001) was used for color development, and the plates were read on an enzyme marker. The results are shown in Table 13 and FIG. 3.

[0491] The results show that 10C9-VH6VL5 mediates the killing of target cells through ADCC effect, and the activity is better than that of 24F4.

[0492] Table 13 ADCC activity of antibodies

[0493] The ADCC activity of Fc mutant antibodies was detected by the above method, the effector cells were NK92 (Huabio), the cell density was adjusted to 1.25 x 10 6 The antibody was diluted to 0.5 μg / mL, and then diluted by 5 times gradient, 20 μL / well was added to the plate, and the results are shown in Table 14.

[0494] The results show that the ADCC activity of Fc mutant antibodies is equivalent to that of 10C9-VH6VL5.

[0495] Table 14 ADCC activity of Fc mutant antibodies

[0496] Example 7 Thermal stability analysis of antibodies

[0497] The thermal stability of the antibodies was detected by detecting the change of tryptophan spontaneous fluorescence intensity in the protein unfolding process using the Nanotemper analysis method. The instrument (Prometheus Pant) was set to start at 25℃, the temperature was raised at a rate of 1℃ / min, and the end temperature was 95℃. After scanning, according to the ratio of tryptophan fluorescence intensity at 350 nm and 330 nm, the thermal denaturation curve and chemical denaturation curve were fitted, and the Tm value was derived, and the results are shown in Table 15.

[0498] The results show that the Tm value of 10C9-VH6VL5 and 10C9-VH6VL5 (LS) is significantly higher than that of 24F4, indicating that the thermal stability of 10C9-VH6VL5 and 10C9-VH6VL5 (LS) is significantly better than that of 24F4.

[0499] Table 15 Thermal stability analysis of antibodies

[0500] Example 8 Detection of endocytosis activity of antibodies

[0501] After cloning the coding sequence of human BDCA2 full-length cDNA (NM_130441.3) and human FcεRIγ (NM_004106.1), HEK293 cells were transfected, and after pressure screening, the cell strain HEK293-hBDCA2 overexpressing human BDCA2 was obtained.

[0502] Antibody endocytosis activity was detected using Incucyte live cell imaging system (Sartorius; Model: Incucyte S3). Trypsin-digested HEK293-hBDCA2 cells were adjusted to a cell density of 1.25 x 10 5 The antibody 24F4 and 10C9-VH6VL5 to be tested were diluted to 1.5 pg / mL and mixed with Incucyte Human Fabfluor-pH Red antibody labeling reagent (Sartorius; Catalog No: 4722) in equal volume. After incubation at room temperature for 20 min, the mixture was added to the overnight cultured cells at 40 pL / well. The cells were placed in the live cell imaging analyzer for reading. The results are shown in Figure 4.

[0503] The results showed that the humanized antibody 10C9-VH6VL5 had higher fluorescence value of endocytosis and stronger endocytosis activity compared with the control antibody 24F4.

Claims

1. An anti-BDCA2 antibody or antigen-binding fragment thereof, comprising a heavy chain variable region and a light chain variable region; wherein: a) the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 in any one of SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 in any one of SEQ ID NO: 61, SEQ ID NO: 25, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64; b) the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 in any one of SEQ ID NO: 31, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 in any one of SEQ ID NO: 38, SEQ ID NO: 21, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42; or c) the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 in any one of SEQ ID NO: 49, SEQ ID NO: 23, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 51, and SEQ ID NO: 52; Preferably, the amino acid sequences of the HCDRs and the LCDRs are determined according to the Kabat, Chothia, AbM, or IMTG numbering system.

2. The anti-BDCA2 antibody or antigen-binding fragment thereof of claim 1, comprising a heavy chain variable region and a light chain variable region; wherein: a) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 14, HCDR2 as set forth in SEQ ID NO: 84, and HCDR3 as set forth in SEQ ID NO: 16; wherein SEQ ID NO: 84 has the general formula TISSGX 13 X 14 YTYYPX 15 SVKG, wherein X 13 is selected from D or E, X 14 is selected from S or A, X 15 is selected from D or E; and the light chain variable region comprises LCDR1 of SEQ ID NO: 85, LCDR2 of SEQ ID NO: 18, and LCDR3 of SEQ ID NO: 19; wherein SEQ ID NO: 85 has the general formula KASESVDYX 16 X 17 ESYVN, wherein X 16 is selected from D or E, X 17 is selected from G or A; b) the heavy chain variable region comprises HCDR1 of SEQ ID NO: 2, HCDR2 of any one of SEQ ID NO: 79, and HCDR3 of SEQ ID NO: 4; and SEQ ID NO: 79 has the general formula SVSSGGSSTYYPX1X2VKG, wherein X1 is selected from D or E, and X2 is selected from S or A; and the light chain variable region comprises LCDR1 of SEQ ID NO: 80, LCDR2 of SEQ ID NO: 81, and LCDR3 of SEQ ID NO: 7; wherein SEQ ID NO: 80 has the general formula X3ASQSVDYX4GX5X6YMN, wherein X3 is selected from K or R, X4 is selected from D or E, X5 is selected from D or E, and X6 is selected from S or A; and SEQ ID NO: 81 has the general formula TASNX7EX8, wherein X7 is selected from L or K, and X8 is selected from S or T; or c) the heavy chain variable region comprises HCDR1 of SEQ ID NO: 8, HCDR2 of SEQ ID NO: 9, and HCDR3 of SEQ ID NO: 10; and the light chain variable region comprises LCDR1 of SEQ ID NO: 82, LCDR2 of SEQ ID NO: 83, and LCDR3 of SEQ ID NO: 13, wherein SEQ ID NO: 82 has the general formula X9ASQSVDYX 10 GDNYIN, wherein X9is selected from K or R, X 10 is selected from D or E; and SEQ ID NO: 83 has the general formula TASNX 11 DX 12 wherein X 11 is selected from L or K, X 12 is selected from S or T; Preferably, a) the heavy chain variable region comprises HCDR1 of SEQ ID NO: 14, HCDR2 of any one of SEQ ID NO: 76, SEQ ID NO: 15, and SEQ ID NO: 75, and HCDR3 of SEQ ID NO: 16; and the light chain variable region comprises LCDR1 of any one of SEQ ID NO: 77, SEQ ID NO: 17, and SEQ ID NO: 78, LCDR2 of SEQ ID NO: 18, and LCDR3 of SEQ ID NO: 19; b) the heavy chain variable region comprises HCDR1 of SEQ ID NO: 2, HCDR2 of any one of SEQ ID NO: 66, SEQ ID NO: 3, and SEQ ID NO: 65, and HCDR3 of SEQ ID NO: 4; and the light chain variable region comprises LCDR1 of SEQ ID NO: 80, LCDR2 of SEQ ID NO: 81, and LCDR3 of SEQ ID NO: 7; wherein the light chain variable region comprises LCDR1 as set forth in any one of SEQ ID NO: 68, SEQ ID NO: 5, SEQ ID NO: 67, SEQ ID NO: 69, and SEQ ID NO: 70, LCDR2 as set forth in SEQ ID NO: 6 or SEQ ID NO: 71, and LCDR3 as set forth in SEQ ID NO: 7; or c) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 8, HCDR2 as set forth in SEQ ID NO: 9, and HCDR3 as set forth in SEQ ID NO: 10; and the light chain variable region comprises LCDR1 as set forth in any one of SEQ ID NO: 72, SEQ ID NO: 11, and SEQ ID NO: 73, LCDR2 as set forth in SEQ ID NO: 12 or SEQ ID NO: 74, and LCDR3 as set forth in SEQ ID NO: 13; more preferably, a-1) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 14, HCDR2 as set forth in SEQ ID NO: 76, and HCDR3 as set forth in SEQ ID NO: 16; and the light chain variable region comprises LCDR1 as set forth in SEQ ID NO: 77, LCDR2 as set forth in SEQ ID NO: 18, and LCDR3 as set forth in SEQ ID NO: 19; a-2) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 14, HCDR2 as set forth in SEQ ID NO: 75, and HCDR3 as set forth in SEQ ID NO: 16; and the light chain variable region comprises LCDR1 as set forth in SEQ ID NO: 17, LCDR2 as set forth in SEQ ID NO: 18, and LCDR3 as set forth in SEQ ID NO: 19; a-3) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 14, HCDR2 as set forth in SEQ ID NO: 76, and HCDR3 as set forth in SEQ ID NO: 16; and the light chain variable region comprises LCDR1 as set forth in SEQ ID NO: 17, LCDR2 as set forth in SEQ ID NO: 18, and LCDR3 as set forth in SEQ ID NO: 19; a-4) the heavy chain variable region comprises HCDR1 as set forth in SEQ ID NO: 14, HCDR2 as set forth in SEQ ID NO: 15, and HCDR3 as set forth in SEQ ID NO: 16; and the light chain variable region comprises LCDR1 as set forth in SEQ ID NO: 17, LCDR2 as set forth in SEQ ID NO: 18, and LCDR3 as set forth in SEQ ID NO: 19; or the light chain variable region comprises LCDR1 as set forth in SEQ ID NO: 17, LCDR2 as set forth in SEQ ID NO: 18, and LCDR3 as set forth in SEQ ID NO: 19; or a-5) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 78, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19; b-1) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 68, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7; b-2) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 3, and HCDR3 set forth in SEQ ID NO: 4; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 67, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7; b-3) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 3, and HCDR3 set forth in SEQ ID NO: 4; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 69, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7; b-4) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 3, and HCDR3 set forth in SEQ ID NO: 4; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 70, LCDR2 set forth in SEQ ID NO: 71, and LCDR3 set forth in SEQ ID NO: 7; b-5) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 65, and HCDR3 set forth in SEQ ID NO: 4; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 68, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7; b-6) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 65, and HCDR3 set forth in SEQ ID NO: 4; and the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 69, a LCDR2 as set forth in SEQ ID NO: 6, and a LCDR3 as set forth in SEQ ID NO: 7; b-7) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 65, and a HCDR3 as set forth in SEQ ID NO: 4; and the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 70, a LCDR2 as set forth in SEQ ID NO: 71, and a LCDR3 as set forth in SEQ ID NO: 7; b-8) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 65, and a HCDR3 as set forth in SEQ ID NO: 4; and the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 5, a LCDR2 as set forth in SEQ ID NO: 6, and a LCDR3 as set forth in SEQ ID NO: 7; b-9) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 3, and a HCDR3 as set forth in SEQ ID NO: 4; and the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 5, a LCDR2 as set forth in SEQ ID NO: 6, and a LCDR3 as set forth in SEQ ID NO: 7; b-10) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 66, and a HCDR3 as set forth in SEQ ID NO: 4; and the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 69, a LCDR2 as set forth in SEQ ID NO: 6, and a LCDR3 as set forth in SEQ ID NO: 7; b-11) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 66, and a HCDR3 as set forth in SEQ ID NO: 4; and the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 70, a LCDR2 as set forth in SEQ ID NO: 71, and a LCDR3 as set forth in SEQ ID NO: 7; or b-12) the heavy chain variable region comprises a HCDR1 as set forth in SEQ ID NO: 2, a HCDR2 as set forth in SEQ ID NO: 66, and a HCDR3 as set forth in SEQ ID NO: 4; and the light chain variable region comprises a LCDR1 as set forth in SEQ ID NO: 5, a LCDR2 as set forth in SEQ ID NO: 6, and a LCDR3 as set forth in SEQ ID NO: 7; c-1) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 8, HCDR2 set forth in SEQ ID NO: 9, and HCDR3 set forth in SEQ ID NO: 10; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 11, LCDR2 set forth in SEQ ID NO: 12, and LCDR3 set forth in SEQ ID NO: 13; c-2) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 8, HCDR2 set forth in SEQ ID NO: 9, and HCDR3 set forth in SEQ ID NO: 10; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 11, LCDR2 set forth in SEQ ID NO: 12, and LCDR3 set forth in SEQ ID NO: 13; or c-3) the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 8, HCDR2 set forth in SEQ ID NO: 9, and HCDR3 set forth in SEQ ID NO: 10; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 73, LCDR2 set forth in SEQ ID NO: 74, and LCDR3 set forth in SEQ ID NO: 13; Most preferably, the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 14, HCDR2 set forth in SEQ ID NO: 76, and HCDR3 set forth in SEQ ID NO: 16; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 77, LCDR2 set forth in SEQ ID NO: 18, and LCDR3 set forth in SEQ ID NO: 19; the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 2, HCDR2 set forth in SEQ ID NO: 66, and HCDR3 set forth in SEQ ID NO: 4; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 68, LCDR2 set forth in SEQ ID NO: 6, and LCDR3 set forth in SEQ ID NO: 7; or the heavy chain variable region comprises HCDR1 set forth in SEQ ID NO: 8, HCDR2 set forth in SEQ ID NO: 9, and HCDR3 set forth in SEQ ID NO: 10; and the light chain variable region comprises LCDR1 set forth in SEQ ID NO: 72, LCDR2 set forth in SEQ ID NO: 12, and LCDR3 set forth in SEQ ID NO:

13.

3. The anti-BDCA2 antibody or antigen-binding fragment thereof of claim 1 or 2, wherein the anti-BDCA2 antibody is a murine, chimeric, or humanized antibody.

4. The anti-BDCA2 antibody or antigen-binding fragment thereof of any one of claims 1 to 3, comprising a heavy chain variable region and a light chain variable region; wherein: a) the heavy chain variable region comprises the amino acid sequence set forth in any one of SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57, or comprises an amino acid sequence having at least 85% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 58, SEQ ID NO: 24, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57; and the light chain variable region comprises the amino acid sequence set forth in any one of SEQ ID NO: 61, SEQ ID NO: 25, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64, or comprises an amino acid sequence having at least 85% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 61, SEQ ID NO: 25, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64; b) the heavy chain variable region comprises the amino acid sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, or comprises an amino acid sequence having at least 85% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 31, SEQ ID NO: 20, SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30; and the light chain variable region comprises the amino acid sequence set forth in any one of SEQ ID NO: 61, SEQ ID NO: 25, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64, or comprises an amino acid sequence having at least 85% sequence identity to the amino acid sequence set forth in any one of SEQ ID NO: 61, SEQ ID NO: 25, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO:

64. the heavy chain variable region comprises an amino acid sequence as set forth in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, or an amino acid sequence having at least 85% sequence identity to an amino acid sequence as set forth in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47; and the heavy chain variable region comprises an amino acid sequence as set forth in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, or an amino acid sequence having at least 85% sequence identity to an amino acid sequence as set forth in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47; and the heavy chain variable region comprises an amino acid sequence as set forth in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47, or an amino acid sequence having at least 85% sequence identity to an amino acid sequence as set forth in any one of SEQ ID NO: 43, SEQ ID NO: 22, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47; and Preferably, a-1) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 58, or an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 58; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 61, or an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 61; a-2) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 53, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 53; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 59; a-3) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 53, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 53; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 60, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 60; a-4) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 54, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 54; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 59; a-5) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 54, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 54; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 60, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 60; a-6) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 55, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 55; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 59; a-7) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 55, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 55; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 60, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 60; a-8) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 56, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 56; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 59; a-9) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 56, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 56; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 60, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 60; a-10) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 57, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 59; a-11) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 57, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 60, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 60; a-12) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 57, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 61, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 61; a-13) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 57, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 62, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 62; a-14) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 57, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 63, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 63; a-15) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 57, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 57; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 64, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 64; a-16) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 58, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 58; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 62, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 62; a-17) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 24, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 24; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 25, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 25; b-1) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 31, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 31; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 38, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 38; b-2) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 28, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 32, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 32; b-3) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 28, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 33, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 33; b-4) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 28, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 34, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 34; b-5) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 28, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 35, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 35; b-6) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 28, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 37, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 37; b-7) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 28, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 39, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 39; b-8) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 28, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 40, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 40; b-9) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 28, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 28; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 41, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 41; b-10) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 29, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 32, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 32; b-11) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 29, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 33, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 33; b-12) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 29, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 34, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 34; b-13) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 29, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 35, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 35; b-14) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 29, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 29; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 36, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 36; b-15) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 30, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 30; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 38, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 38; b-16) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 30, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 30; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 39, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 39; b-17) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 30, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 30; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 40, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 40; b-18) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 30, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 30; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 41, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 41; b-19) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 31, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 31; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 39, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 39; b-20) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 31, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 31; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 40, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 40; b-21) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 31, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 31; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 41, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 41; b-22) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 31, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 31; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 42, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 42; or b-23) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 20, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 20; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 21, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 21; c-1) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 43, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 43; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 49, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 49; c-2) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 43, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 43; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 50, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 50; c-3) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 44, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 44; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 48, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 48; c-4) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 44, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 44; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 49, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 49; c-5) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 44, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 44; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 50, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 50; c-6) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 45, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 45; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 48, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 48; c-7) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 45, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 45; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 49, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 49; c-8) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 45, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 45; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 50, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 50; c-9) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 46, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 46; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 51, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 51; c-10) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 46, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 46; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 52, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 52; c-11) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 47, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 47; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 51, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 51; c-12) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 47, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 47; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 52, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 52; or c-13) the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 22, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 22; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 23, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 23; More preferably, the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 58, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 58; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 61, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 61; the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 31, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 31; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 38, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 38; or the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 43, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 43; and the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 49, or an amino acid sequence that has at least 85% sequence identity to SEQ ID NO:

49.

5. The anti-BDCA2 antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antigen-binding fragment is selected from any one of a Fab, a scFv, a Fv, a Fab’, a F(ab’)2, a single domain antibody, a scFab, a linear antibody, and a multispecific antibody.

6. The anti-BDCA2 antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, further comprising a heavy chain constant region and / or a light chain constant region; preferably, the heavy chain constant region is selected from the group consisting of a constant region of human IgGl, human IgG2, human IgG3 and human IgG4 or a mutant thereof; more preferably, the mutant of the heavy chain constant region comprises mutations that prolong the half-life of the antibody; and / or the light chain constant region is selected from the group consisting of a lambda light chain constant region and a kappa light chain constant region.

7. The anti-BDCA2 antibody or antigen-binding fragment thereof according to claim 6, wherein: the mutant of the heavy chain constant region has Y at position 252, T at position 254 and E at position 256, or the mutant of the heavy chain constant region has L at position 428 and S at position 434, the amino acid positions being determined by EU numbering; preferably, the heavy chain constant region is a constant region of human IgGl or a mutant thereof comprising M252Y, S254T and T256E mutations according to EU numbering, or comprising M428L and N434S mutations; more preferably, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 26 or a mutant thereof comprising M252Y, S254T and T256E mutations according to EU numbering, or comprising M428L and N434S mutations, and the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 27; most preferably, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 93 or SEQ ID NO: 92, and the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO:

27.

8. The anti-BDCA2 antibody or antigen-binding fragment thereof according to any one of claims 1 to 7, comprising a heavy chain and a light chain, wherein: a-1) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 90 or an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 90, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 91 or an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 91; a-2) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 94 or an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 94, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 91 or an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 91; a-3) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 96 or an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 96, and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 91 or an amino acid sequence having at least 80% sequence identity to SEQ ID NO:

91. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ b-1) the heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 86, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 86, and the light chain comprises an amino acid sequence as set forth in SEQ ID NO: 87, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 87; b-2) the heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 97, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 97, and the light chain comprises an amino acid sequence as set forth in SEQ ID NO: 87, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 87; b-3) the heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 98, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 98, and the light chain comprises an amino acid sequence as set forth in SEQ ID NO: 87, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 87; c-1) the heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 88, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 88, and the light chain comprises an amino acid sequence as set forth in SEQ ID NO: 89, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 89; c-2) the heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 99, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 99, and the light chain comprises an amino acid sequence as set forth in SEQ ID NO: 89, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 89; or c-3) the heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 95, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 95, and the light chain comprises an amino acid sequence as set forth in SEQ ID NO: 89, or an amino acid sequence that has at least 80% sequence identity to SEQ ID NO:

89.

9. A pharmaceutical composition comprising: 1) an anti-BDCA2 antibody or antigen-binding fragment thereof of any one of claims 1 to 8, and 2) one or more pharmaceutically acceptable carriers, diluents, buffers, or excipients.

10. An isolated nucleic acid encoding: an anti-BDCA2 antibody or antigen-binding fragment thereof of any one of claims 1 to 8.

11. An expression vector comprising the isolated nucleic acid of claim 10.

12. A host cell comprising: the isolated nucleic acid of claim 10, or the expression vector of claim 11.

13. A method of treating and / or preventing a disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of the anti-BDCA2 antibody or antigen-binding fragment thereof of any one of claims 1 to 8, or a therapeutically effective amount of the pharmaceutical composition of claim 9; preferably, the disease is an inflammatory disease or an autoimmune disease; more preferably, the inflammatory disease or autoimmune disease is selected from: Systemic lupus erythematosus, discoid lupus, lupus nephritis, cutaneous lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, systemic sclerosis (scleroderma), psoriasis, psoriatic arthritis, type I diabetes, fibrosis (e.g., skin fibrosis, lung fibrosis), pemphigus vulgaris, Graves’ disease, scleroderma (localized scleroderma), Sjogren’s disease, Hashimoto’s disease, dermatomyositis, polymyositis, asthma, Behcet’s disease, Crohn’s disease, autoimmune glomerulonephritis, membranous glomerulopathy, juvenile rheumatoid arthritis, mixed connective tissue disease, multiple sclerosis, nephrotic syndrome, panniculitis, pemphigoid, pemphigus, pemphigus erythematosus, pemphigus foliaceus, pemphigus vulgaris, polymyalgia rheumatica, Raynaud’s phenomenon / syndrome, Sjogren’s syndrome, and ulcerative colitis.

14. A method of inducing death of plasmacytoid dendritic cells in a subject, the method comprising contacting a plasmacytoid dendritic cell expressing BDCA2 with the anti-BDCA2 antibody or antigen-binding fragment thereof of any one of claims 1 to 8, or the pharmaceutical composition of claim 9.

15. A method of reducing production of inflammatory cytokines or chemokines by plasmacytoid dendritic cells in a subject, the method comprising contacting a plasmacytoid dendritic cell expressing BDCA2 with an amount of the anti-BDCA2 antibody or antigen-binding fragment thereof of any one of claims 1 to 8, or the pharmaceutical composition of claim 9; preferably, the inflammatory cytokines or chemokines are selected from type I interferons, IL-6, TNF-a, CCL3, CCL4, IP10, and RANTES.

Images