SUSCEPTIBILITY TO RHEUMATOID-ARTHRITIS MAPS TO A T-CELL EPITOPE SHARED BY THE HLA-DW4 DR BETA-1 CHAIN AND THE EPSTEIN-BARR VIRUS GLYCOPROTEIN GP110

SUSCEPTIBILITY TO RHEUMATOID-ARTHRITIS MAPS TO A T-CELL EPITOPE SHARED BY THE HLA-DW4 DR BETA-1 CHAIN AND THE EPSTEIN-BARR VIRUS GLYCOPROTEIN GP110
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DOI:
10.1073/pnas.86.13.5104
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发表时间:
1989-07-01
影响因子:
11.1
通讯作者:
CARSON, DA
CARSON, DA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
ROUDIER, J;PETERSEN, J;CARSON, DA

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类风湿性关节炎与人类白细胞抗原-DR4有关。疾病易感性映射到位于DRβ-1链第三高变区的氨基酸序列QKRAA。这一区域被认为是T细胞抗原受体的识别部位。我们在人类环境中寻找一种可以诱导T细胞识别该序列的抗原。蛋白质和DNA数据库的分析表明,由BALF4开放阅读框编码的Epstein-Barr病毒糖蛋白gp110含有与类风湿关节炎易感决定因素高度同源的序列QKRAAQRAA。利用合成肽的抗体进行的实验表明,QKRAA决定簇在gp110蛋白上表达。有Epstein-Barr病毒感染血清学证据的人有抗gp110的血清抗体和识别gp110和包含QKRAA决定簇的HLA-Dw4的外周血T细胞。
Rheumatoid arthritis is associated with the HLA antigen HLA-DR4. Disease susceptibility maps to the amino acid sequence QKRAA located in the third hypervariable region of the DR .beta.-1 chain. This region is thought to be a site of recognition for the T-cell antigen receptor. We searched for an antigen in the human environment that could induce T-cell recognition of this sequence. An analysis of protein and DNA databases revealed that the Epstein-Barr virus glycoprotein gp110, which is encoded by the BALF4 open reading frame, contains the sequence QKRAAQRAA, which is highly homologous to the rheumatoid arthritis susceptibility determinant. Experiments using antibodies to synthetic peptides showed that the QKRAA determinant is expressed on the gp110 protein. Humans with serologic evidence of Epstein-Barr virus infection had serum antibodies to gp110 and peripheral blood T cells that recognized peptides from gp110 and HLA-Dw4 encompassing the QKRAA determinant.