与来自人胶原蛋白II的肽复合的HLA - DR4（DRA0101，DRB10401）的X射线晶体结构。

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

作者信息

Dessen A, Lawrence C M, Cupo S, Zaller D M, Wiley D C

机构信息

Laboratory of Molecular Medicine, The Children's Hospital, Boston, Massachusetts 02115, USA.

出版信息

Immunity. 1997 Oct;7(4):473-81. doi: 10.1016/s1074-7613(00)80369-6.

DOI:10.1016/s1074-7613(00)80369-6

PMID:9354468

Abstract

Genetic predisposition to rheumatoid arthritis (RA) is linked to the MHC class II allele HLA-DR4. The charge of the amino acid at DRbeta71 in the peptide-binding site appears to be critical in discriminating DR molecules linked to increased disease susceptibility. We have determined the 2.5 A 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 DRbeta71 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.

摘要

类风湿关节炎（RA）的遗传易感性与MHC II类等位基因HLA - DR4相关。肽结合位点中DRβ71处氨基酸的电荷在区分与疾病易感性增加相关的DR分子方面似乎至关重要。我们已经确定了与RA关联最强的DR4分子（DRB1*0401）与人类胶原蛋白II肽复合的2.5埃X射线结构。DRβ71赖氨酸与P4肽位置的天冬氨酸之间预测盐桥的细节表明了它可能如何参与抗原结合和TCR激活。本文提出了一个关于DR4识别胶原蛋白II（261 - 273）的模型，胶原蛋白II是人类转基因RA小鼠模型中的免疫显性抗原。