67 results about "Cdr3 region" patented technology

The present invention relates to a polypeptide construct comprising at least one CDR3 region, wherein at least one of the at least CDR3 regions comprises at least one substitution in the amino acid sequence YYDDHY (SEQ ID NO.1) and wherein the at least one substitution comprises: in the first position of SEQ ID NO.1 a substitution from Y to H; in the second position of SEQ ID NO. 1 a substitution from Y to S, from Y to N, from Y to F or from Y to H; in third position of SEQ ID NO. 1 a substitution from D to N or from D to E; in the forth position of SEQ ID NO. 1 a substitution from D to Q, from D to A, from D to V, from D to E or from D to G; in the fifth position of SEQ ID NO. 1 a substitution from H to Q, from H to P, from H to Y, from H to R or from H to N; or in the sixth position a substitution from Y to N.

Disclosed are: a nucleotide sequence and an amino acid sequence for CDR3 region of T-cell receptor (TCR) gene of WT1-specific cytotoxic T-cell (CTL) for WT1 protein; a method for the detection or treatment of cancer using the nucleotide sequence or the amino acid sequence; and a chip, a primer set, a kit, an apparatus and the like for use in the detection of cancer, each of which comprises the nucleotide sequence or the amino acid sequence.

The invention provides dyes, biosensors, and methods for using the dyes and biosensors to detect selected target molecules. The biosensors have a binding domain and a dye, or a dye which is attached directly to the target of interest. Binding domains contemplated by the invention include biomolecules or fragments of biomolecules that interact with target molecules of interest and can be specific to a given conformational state or covalent modification of the molecule (e.g. phosphorylation). In one embodiment, the binding domain of a biosensor is a single chain variable fragment (scFv) with a dye of the invention linked to a CDR3 region. The invention also provides environmentally sensitive dyes useful for detecting changes in the binding, conformational change, or posttranslational modification of the selected target.

The present invention provides a humanized antibody or fragment thereof specific for the antigen CD45R0, wherein said antibody or fragment thereof comprises a humanized heavy chain variable domain comprising a CDR1 region of SEQ ID NO:1, a CDR2 region of SEQ ID NO:2, and a CDR3 region of SEQ ID NO:3, and a humanized light chain variable domain comprising a CDR1 region of SEQ ID NO:4, a CDR2 region of SEQ ID NO:5, and a CDR3 region of SEQ ID NO:6. It is also provided the use of the present antibody or fragment thereof for enrichment or depletion of CD45R0-expressing cells from a sample comprising CD45R0-expressing cells.

The invention is in the field of medical treatment and prevention. The invention provides an antibody or a part thereof capable of specifically binding to the Hepatitis B surface antigen (HBsAg) and having Hepatitis B Virus (HBV) neutralizing activity, wherein said antibody or fragment thereof comprises a light chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 6, a light chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 7, a heavy chain CDR1 region comprising the amino acid sequence of SEQ ID NO: 8, a heavy chain CDR2 region comprising the amino acid sequence of SEQ ID NO: 9 and a heavy chain CDR3 region comprising the amino acid sequence of SEQ ID NO: 10.

The invention discloses a method for simultaneously sequencing a multi-sample CDR3 (complementary determining region 3) receptor library with a high flux, comprising the following steps of: only designing one set of V-gene family upstream primers in the variable region of a TCR (T cell antigen receptor) or BCR (B cell antigen receptor) chain according to the homology of the V-gene family, then designing C or J gene characteristic downstream primers of the TCR or BCR chain as many as samples and suitable for being paired with the upstream primers, amplifying each sample by one characteristic downstream primer and the same set of upstream primers to obtain a CDR3 region of the TCR or BCR, then mixing all the amplified samples to be a to-be-sequenced sample library, finally sequencing, wherein the characteristic downstream primers are designed by different ATCG basic group compositions. The CDR3 sequences of multiple samples can be simultaneously sequenced by operating one high-flux sequencing program via the method for simultaneously sequencing a multi-sample CDR3 receptor library with a high flux disclosed by the invention, so that the high-flux sequencing cost is greatly decreased. Thus, a high-flux sequencing technology has a wide application value in a sequencing research of a CDR3 receptor library.

The present invention provides a humanized antibody or fragment thereof specific for the antigen CD45R0, wherein said antibody or fragment thereof comprises a humanized heavy chain variable domain comprising a CDR1 region of SEQ ID NO:1, a CDR2 region of SEQ ID NO:2, and a CDR3 region of SEQ ID NO:3, and a humanized light chain variable domain comprising a CDR1 region of SEQ ID NO:4, a CDR2 region of SEQ ID NO:5, and a CDR3 region of SEQ ID NO:6. It is also provided the use of the present antibody or fragment thereof for enrichment or depletion of CD45R0-expressing cells from a sample comprising CD45R0-expressing cells.

There is disclosed a polypeptide consisting of between 7 and 100 amino acids and comprising: the sequence of the peptide of any one of SEQ. ID NOS: 1 to 145. There is also disclosed a T-cell receptor, or a peptide-binding fragment thereof, wherein the CDR3 region of the beta chain of the T-cell receptor comprises a glycine residue at position 5 from the N-terminus. The T-cell receptor is capable of binding a peptide consisting of the sequence of SEQ. ID NO. 18, when the peptide is presented on an HLA molecule of a first HLA allele.

The invention belongs to the technical field of biology and specifically relates to an antigenic epitope displaying method based on a single domain antibody. Specifically, an exogenous antigenic epitope is displayed in a CDR3 region of the single domain antibody, and the single domain antibody skeleton protein which displays the exogenous antigenic epitope on the surface of a molecule can be used for preparing an antibody with a too small epitope, be also used as a substitutive antigen of an exogenous antigen and used for immunizing animals and preparing antibodies aiming at the exogenous antigen. In addition, the antigenic epitope displaying method based on a single domain antibody skeleton can also be used for preparing epitope vaccins.

The invention discloses a CD22 single domain antibody, a nucleotide sequence, a reagent kit, a CAR-T virus vector and a CAR-T cell. The amino acid sequences of the CD22 single domain antibody sequentially comprise FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4 regions, wherein the FR1, FR2, FR3 and FR4 regions are framework region amino acid sequences, the CDR1, CDR2 and CDR3 regions are variable regionamino acid sequences, and the amino acid sequences are shown as table 1. According to the technical scheme, through a method combining genetic engineering, the single domain antibody of specific binding CD22 protein is obtained. The antibody specificity combination CD22 protein is high in specific binding capacity and high in affinity.

The invention provides an antibody or an antigen bound part which is specifically bound to a human papilloma virus low-risk sub type-type 6 L1 protein and / or VLP. The antibody or the antigen bound part comprises CDR1, CDR2 and CDR3 regions of a heavy chain variable region shown in SEQ ID NO. 1-3 and CDR1, CDR2 and CDR3 regions of a light chain variable region shown in SEQ ID NO. 4-6. The antibody or the antigen bound part which is specifically bound with the human papilloma virus low-risk sub type-type 6 L1 protein and / or VLP has no cross reactions with most of other HPV sub types such as HPV11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 and the like, is high in specificity, has a characteristic of neutralizing a HPV6 pseudovirus and blocking infection of the pseudovirus, and is high in affinity. A twin-antibody sandwiched ELISA detection kit established by two antibodies can be used for detecting the presence or level of HPV6L1 protein and the antibody can be further used for treatment of patients and passive immunity of susceptible population and has a good application prospect.

The invention relates to human neutralizing anti-KIT antibodies and uses thereof. More particularly, the invention relates to an antibody comprising a heavy chain variable region comprising SEQ ID NO: 2 in the H-CDR1 region, SEQ ID NO: 3 in the H-CDR2 region and SEQ ID NO: 4 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 6 in the L-CDR1 region, SEQ ID NO: 7 in the L-CDR2 region and SEQ ID NO: 8 in the L-CDR3 region. The invention also relates to an antibody comprising a heavy chain variable region comprising SEQ ID NO: 10 in the H-CDR1 region, SEQ ID NO: 11 in the H-CDR2 region and SEQ ID NO: 12 in the H-CDR3 region; and a light chain variable region comprising SEQ ID NO: 14 in the L-CDR1 region, SEQ ID NO: 15 in the L-CDR2 region and SEQ ID NO: 16 in the L-CDR3 region.

The current invention provides methods to identify γ9δ2T-cell receptors (γ9δ2TCR) that mediate anti-tumour responses. Surprisingly, it was now found that the CDR3 regions of the γ9-T-cell receptor chain and the δ2-T-Cell receptor chain (δ2TCR chain) are of importance. Based on these findings, combinatorial-γδTCR-chain-exchange (CTE) is proposed as an efficient method for identifying γ9δ2TCRs that mediate anti-tumour responses. Using the method of the invention, specific sequences of the respective γ9TCR and δ2TCR chains were identified that mediate anti-tumour responses. Hence, the invention further provides for specific γ9δ2TCRs, or fragments thereof, that may be used e.g. in diagnostics or treatment of cancer. The invention further provides for nucleic acid sequences, genetic constructs and retroviral vectors that can be used to express the γ9δ2TCRs according to the invention.

The invention provides an anti-PD-L1 nano antibody and application thereof. The sequence of the antibody comprises an FR region, a CDR region and an HV region, wherein the FR region comprises an FR1 region with an amino acid sequence as shown in SEQ ID NO.1, an FR2 region with an amino acid sequence as shown in SEQ ID NO.2, an FR3 region with an amino acid sequence as shown in SEQ ID NO.3 and an FR4 region with an amino acid sequence as shown in SEQ ID NO.4; the CDR region comprises a CDR1 region with an amino acid sequence shown as SEQ ID NO.5 and a CDR3 region with an amino acid sequence shown as any one of SEQ ID NO.8 to SEQ ID NO.12; and the HV region comprises an HV2 region with an amino acid sequence as shown in SEQ ID NO.6 and an HV4 region with an amino acid sequence as shown in SEQ ID NO.7. The anti-PD-L1 nano antibody screened on the basis of the novel shark V-NAR framework sequence has excellent stability and can provide a new variety for research, development and acquisition of novel antitumor drugs.

The invention discloses an antibody specially bound with Norovirus GII.4 genotype VP1 protein and / or VLP. The antibody comprises CDR1, CDR2 and CDR3 regions of a heavy chain variable region shown in SEQ ID NO. 1-3 and / or The CDR1, CDR2 and CDR3 regions of the light chain variable region shown in SEQ ID NO. 4-6. The antibody or antigen binding part of Norovirus GII.4 genotype VP1 protein and / or VLPprovided by the present invention, has no cross-reaction with GI.1 genotype, is high in specificity, has the characteristic of blocking binding between Norovirus GII.4 genotype VP1 protein and / or VLPand HBGA, is high in affinity, can be used for detecting the presence or level of Norovirus GII.4 genotype VP1 protein and / or VLP in a sample developing kits, as well as treating patients and performing passive immunization on susceptible populations, and has good application prospect.

The invention discloses an antibody specifically binding to CD123. The antibody comprises: a) CDR1, CDR2 and CDR3 regions of a heavy-chain variable region shown as SEQ ID No. 1 to 3 or regions 80% or more homogeneous with the CDR1, CDR2 and CDR3 regions; or b) CDR1, CDR2 and CDR3 regions of a heavy-chain variable region shown as SEQ ID No. 4 to 6 or regions 80% or more homogeneous with the CDR1, CDR2 and CDR3 regions; or c) CDR1, CDR2 and CDR3 regions of a heavy-chain variable region shown as SEQ ID No. 7 to 9 or regions 80% or more homogeneous with the CDR1, CDR2 and CDR3 regions. The monoclonal antibody can be used for detecting cells expressing CD123, and can also be applied to tumor immunotherapy independently or be applied to tumor immunotherapy in combination with other methods; that is, the monoclonal antibody can be effectively applied to preparation of drugs for treating tumors, infectious diseases and autoimmune diseases, resisting immunological rejection and the like.

The invention discloses a method for simultaneously sequencing a multi-sample CDR3 (complementary determining region 3) receptor library with a high flux, comprising the following steps of: only designing one set of V-gene family upstream primers in the variable region of a TCR (T cell antigen receptor) or BCR (B cell antigen receptor) chain according to the homology of the V-gene family, then designing C or J gene characteristic downstream primers of the TCR or BCR chain as many as samples and suitable for being paired with the upstream primers, amplifying each sample by one characteristic downstream primer and the same set of upstream primers to obtain a CDR3 region of the TCR or BCR, then mixing all the amplified samples to be a to-be-sequenced sample library, finally sequencing, wherein the characteristic downstream primers are designed by different ATCG basic group compositions. The CDR3 sequences of multiple samples can be simultaneously sequenced by operating one high-flux sequencing program via the method for simultaneously sequencing a multi-sample CDR3 receptor library with a high flux disclosed by the invention, so that the high-flux sequencing cost is greatly decreased. Thus, a high-flux sequencing technology has a wide application value in a sequencing research of a CDR3 receptor library.

The invention discloses an antibody capable of realizing specific binding with norovirus GI.1 gene type VP1 protein and / or VLP, and a preparation method and applications thereof. The antibody containsCDR1, CDR2 and CDR3 zones containing heavy chain variable regions represented by SEQ ID NO.1-3, and / or CDR1, CDR2 and CDR3 zones containing light chain variable regions represented by SEQ ID NO.4-6.No cross reaction of the norovirus GI.1 gene type VP1 protein and / or VLP antibody or an antigen binding part with GII.4 gene type is caused; the specificity is high; the antibody is capable of blocking binding of norovirus GI.1 gene type VP1 protein and / or VLP with HBGA; the endophilicity is high; the antibody can be used for research and development of kits used for detecting existing or contentof norovirus GI.1 gene type VP1 protein and / or VLP in samples, and treatment on patients and passive immunity on susceptible population, and is promising in application prospect.

An artificial antibody library with a super-repertory (1011 or more) is constructed by: using a cDNA library as a template, amplifying a fragment containing the CDR1 and CDR2s regions of the VH or VL region of immunoglobulin gene and a fragment containing the CDR3 region each by the PCR method; integrating the VH library and the VL library, which are little contaiminated with unexpressionable repertory and have high safety, into an nono-expression vector; transferring it into a host; and then shuffling the VH region in the VH library with the VL region in the VL library.

The invention relates to a method for constructing a mouse TCR alpha CDR3 region sequencing library. The method mainly comprises the following steps: (1) extracting total RNA from mouse tissues or whole blood; (2) reversely transcribing the RNA into cDNA, ligating a linker sequence to the end of the long-stranded cDNA, and amplifying TCR alpha containing a CDR3 region through a universal C-terminal primer and a linker sequence primer; (3) fragmenting the TCR alpha through Tn5 transposase, and enriching a CDR3 region sequence; and (4) carrying out sequencing by an illumina high-throughput sequencing platform. The method is suitable for library construction of tissues containing various types of T cells, and body fluids, can highly-efficiently amplify the mouse TCR alpha through a 5'RACE technology in an agonic manner, and solves the problems of difficulty in control of the template copy number and the offset of the product, caused by multiplex PCR amplification; and the Tn5 enzyme's ability to simultaneously complete DNA fragmentation and linker ligation and a specific primer are used to fast and accurately enrich and construct a library of the hypervariable region (CDR3 region) ofthe TCR alpha, so pertinent sequencing, easy data analysis and sequencing cost saving are achieved.

The invention relates to a method for constructing a human TCR alpha CDR3 region sequencing library. The method mainly comprises the following steps: (1) extracting total RNA from human tissues or whole blood; (2) reversely transcribing the RNA into cDNA, ligating a linker sequence to the end of the long-stranded cDNA, and amplifying TCR alpha containing a CDR3 region through a universal C-terminal primer and a linker sequence primer; (3) fragmenting the TCR alpha through Tn5 transposase, and enriching a CDR3 region sequence; and (4) carrying out sequencing by an illumina high-throughput sequencing platform. The method is suitable for library construction of tissues and body fluids, containing various types of T cells, can highly-efficiently amplify the human TCR alpha through a 5'RACE technology in an agonic manner, and solves the problems of difficulty in control of the template copy number and the offset of the product, caused by multiplex PCR amplification; and the Tn5 enzyme's ability to simultaneously complete DNA fragmentation and linker ligation and a specific primer are used to fast and accurately enrich and construct a library of the hypervariable region (CDR3 region) ofthe TCR alpha, so pertinent sequencing, easy data analysis and sequencing cost saving are achieved.

Disclosed is a human monoclonal antibody, wherein said antibody comprises: a heavy chain CDR1 region comprising amino acid sequence SEQ ID NO: 296; a heavy chain CDR2 region comprising amino acid sequence SEQ ID NO: 297; a heavy chain CDR3 region comprising amino acid sequence SEQ ID NO: 298; a light chain CDR1 region comprising amino acid sequence SEQ ID NO: 299; a light chain CDR2 region comprising amino acid sequence SEQ ID NO: 300; a light chain CDR3 region comprising amino acid sequence SEQ ID NO: 301; characterized in that said antibody has opsonic phagocytic killing activity against at least one strain of each of at least two different Enterococcus species and against at least one strain of Staphylococcus aureus.

The invention discloses a CD123 single domain antibody, a nucleic acid sequence, an expression vector and a kit. An amino acid sequence of the CD123 single domain antibody includes an FR1 region, a CDR1 region, an FR2 region, a CDR2 region, an FR3 region, a CDR3 region and an FR4 region which are formed in sequence, wherein the FR1 region, the FR2 region, the FR3 region and the FR4 region are composed of frame-region amino acid sequences, the CDR1 region, the CDR2 region and the CDR3 region are composed of variable-region amino acid sequences, and the amino acid sequences of the FR1 region, the CDR1 region, the FR2 region, the CDR2 region, the FR3 region, the CDR3 region and the FR4 region are shown in a table 1. According to the technical scheme, in combination with a genetic engineeringmethod, the single domain antibody capable of specifically binding to a CD123 protein is obtained, and the single domain antibody has high specific binding capability of specifically binding to the CD123 protein and high affinity.

The present invention provides a humanized antibody or fragment thereof specific for the antigen CD3, wherein said antibody or fragment thereof comprises a heavy chain variable domain comprising a CDR1 region of SEQ ID NO: 1, a CDR2 region of SEQ ID NO:2, and a CDR3 region of SEQ ID NO:3, and a light chain variable domain comprising a CDR1 region of SEQ ID NO:4, a CDR2 region of SEQ ID NO:5, and aCDR3 region of SEQ ID NO:6. In addition, the present invention provides a method for polyclonal stimulation of T cells comprising contacting a population of T cells with said anti-CD3 antibody, optionally with an anti-CD28 antibody, wherein said anti-CD3 antibody and optionally said anti-CD28 antibody are linked to particles. Further said anti-CD3 antibody can be used for reversible tagging of cells.

An agonistic 4-1BB monoclonal antibody or an antigen binding fragment thereof, comprising a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising: a CDR1 region having an amino acid sequence as shown in SEQ ID NO: 1, a CDR2 region having an amino acid sequence as shown in SEQ ID NO: 2, and a CDR3 region having an amino acid sequence as shown in SEQ ID NO: 3, the light chain variable region comprising: a CDR1 region having an amino acid sequence as shown in SEQ ID NO: 4, a CDR2 region having an amino acid sequence as shown in SEQ ID NO: 5, and a CDR3 region having an amino acid sequence as shown in SEQ ID NO: 6. The monoclonal antibody is targeted towards h4-1BB, and specifically binds to h4-1BB so as to activate T cells. The monoclonal antibody has application potential for treating a variety of cancers by means of an immunomodulatory effect.

Changes in adaptive immune system were identified and correlated as a predictor of Aβ40 and Aβ42 and AD progression. T-cell, B-cell, TCR and BCR profiles were used to correlate clinical progression of AD. The CDR3 region was spectratyped, showing the clonality of the CDR3 region. This intrafamily gene fragment length profile was compared to age-matched controls, thereby indicating the existence of a neurodegenerative disease. The novel method is useful in diagnosing neurodegenerative disease, like Parkinson's disease, HIV-associated Dementia, or Alzheimer's disease. Moreover, this permits the clinical identification of patients at a very early stage of AD and / or monitoring the potential benefits of disease modifying therapeutics.