X-ray crystal structure of HLA-DR4 (DRA0101, DRB10401) complexed with a peptide from human collagen II

被引：311

作者：

Dessen, A

Lawrence, CM

Cupo, S

Zaller, DM

Wiley, DC

机构：

[1] CHILDRENS HOSP,MOL MED LAB,BOSTON,MA 02115

[2] CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115

[3] HARVARD UNIV,DEPT MOL & CELLULAR BIOL,CAMBRIDGE,MA 02138

[4] MERCK RES LABS,MOL IMMUNOL,RAHWAY,NJ 07065

来源：

IMMUNITY | 1997年 / 7卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S1074-7613(00)80369-6

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Genetic predisposition to rheumatoid arthritis (RA) is linked to the MHC class II allele HLA-DR4. The charge of the amino acid at DR beta 71 in the peptide-binding site appears to be critical in discriminating DR molecules linked to increased disease susceptibility. We have determined the 2.5 Angstrom x-ray structure of the DR4 molecule with the strongest linkage to RA (DRB1*0401) complexed with a human collagen II peptide. Details of a predicted salt bridge between lysine DR beta 71 and aspartic acid at the P4 peptide position suggest how it may participate in both antigen binding and TCR activation. A model is proposed for the DR4 recognition of collagen II (261-273), an antigen immunodominant in human-transgenic mouse models of RA.

引用

页码：473 / 481

页数：9

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