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Identification of broadly reactive DR restricted epitopes

A primary and auxiliary technology, applied in the direction of medical preparations containing active ingredients, receptors/cell surface antigens/cell surface determinants, specific peptides, etc., can solve problems such as laborious alleles

Inactive Publication Date: 2000-04-19
埃皮缪纳股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

To date, however, a general method for their identification has not been developed, which may at least reflect the fact that quantitative DR binding assays are laborious and the large number of alleles must be taken into account

Method used

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  • Identification of broadly reactive DR restricted epitopes
  • Identification of broadly reactive DR restricted epitopes
  • Identification of broadly reactive DR restricted epitopes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0061] Materials and methods

[0062] cell. The following Epstein-Barr virus (EBV)-transformed homozygous cell lines were used as a source of human HLA class II molecules: LG2[DRB1c0101(DR1)1; GM3107[DRB50101(DR2w2a)]; MAT(DRB10301(DR3)1; PREISS[DRB 10401 (DR4w4)1; BIN40[DRB10404(DR4w14)1; SWEIG[DRB11101(DR5w11)]; PIOUT[DRB10701(DR7)](a); KT3[DRB0405(DR4w15)]; Herluf[DRB11201(DR5w12)]; HO301[ DRB11302(DR6w19)]; OLL[DRB10802(DR8w2)]; and HTC9074[DRB10901(DR9), generously provided by Dr. Paul Harris, Columbia University]. In some cases, transfected fibroblasts were employed: L466.1[ DRB11501(DR2w2b)]; TR81.19[DRB30101(DR52a)]; and L257.6[DRB40101(DRw53)].(Valli et al., J.Clin.Invest.91:616(1993)). Cells were cultured in They were maintained in vitro in RPMI 1640 medium supplemented with 2 mM L-glutamine [GIBCO, Grand Island, NY], 50 μM 2-ME, and 10% heat-inactivated FCS [Irvine Scientific, Santa Ana, CA]. Cells were also supplemented with 100 μg / ml streptomycin and 100 U / ml p...

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Abstract

The present invention is based on peptide binding specificities of HLA DR4w4, DR1 and DR7. Peptides binding to these DR molecules have a motif characterized by a large aromatic or hydrophobic residue in position 1 (Y, F, W, L, I, V, M) and a small, non charged residue in position 6 (S, T, C, A, P, V, I, L, M). In addition, allele-specific secondary effects and secondary anchors are defined, and these results were utilized to derive allele specific algorithms. By the combined use of such algorithms peptides capable of degenerate DR1, 4, 7 binding were identified.

Description

[0001] Cross References to Related Applications [0002] The present application is a continuation-in-part of USSN 60 / 036,713, filed January 23, 1997, and USSN 60 / 037,432, filed February 7, 1997, both of which are incorporated herein by reference. Background of the invention [0003] Helper (sex) T lymphocytes (HTL) play a variety of important functions in the immunity to pathogens. First, they help induce CTL and antibody responses. Through direct contact and through the secretion of lymphokines such as IL2 and IL4, HTL supports and promotes the expansion and differentiation of T and B cell precursors into effector cells. In addition, HTLs may themselves be effector cells, and this activity is also mediated by direct cell contact and secretion of lymphokines such as IFN-γ and TNFα. HTL has been shown to have direct effector activity in tumors as well as in the context of viral, bacterial, parasitic and fungal infections. [0004] HTL recognizes complexes of MHC class II mo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/09A61K31/7088A61K38/00A61K39/00A61K48/00A61P31/00C07K7/00C07K14/00C07K14/005C07K14/02C07K14/16C07K14/18C07K14/44C07K14/445C07K14/725C07K14/74G01N33/569
CPCC12N2770/24244C12N2740/16222C07K14/001G01N2333/70539C12N2740/16122C07K14/70539C12N2730/10122C12N2740/16322G01N33/56977C12N2770/24222Y10S530/868C07K14/005C07K14/445A61K38/00A61K48/00A61K39/00A61P31/00Y02A50/30
Inventor A·塞特J·悉尼S·索思伍德
Owner 埃皮缪纳股份有限公司
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