The 1.5 Å crystal structure of a highly selected antiviral T cell receptor provides evidence for a structural basis of immunodominance
The 1.5 Å crystal structure of a highly selected antiviral T cell receptor provides evidence for a structural basis of immunodominance
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DOI：
10.1016/s0969-2126(02)00878-x
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发表时间：
2002-11-01
期刊：
影响因子：
5.7
通讯作者：
Rossjohn, J
中科院分区：
文献类型：
--
作者：
Kjer-Nielsen, L;Clements, CS;Rossjohn, J
尽管有>10（15）个α T细胞受体（TcR）的潜在库，但对EB病毒（EBV）的潜伏抗原的HLA B8限制性溶细胞T细胞应答在所选择的TcR序列中显著受限。即使在不相关的个体中，这种反应也由单一的高度限制性TcR克隆型主导，该克隆型选择高变Valpha、Vbeta、D、J和N区基因的相同组合。我们已经确定了这种“公共”TcR的1.5埃晶体结构，揭示了六个高变环中的五个采用了新颖的构象，提供了独特的结合位点，其中包含一个预计覆盖HLA B8-肽复合物的深口袋。研究结果表明，这种克隆型的免疫优势的免疫反应EBV的结构基础。
Despite a potential repertoire of >10(15) alphabeta T cell receptors (TcR), the HLA B8-restricted cytolytic T cell response to a latent antigen of Epstein-Barr virus (EBV) is strikingly limited in the TcR sequences that are selected. Even in unrelated individuals this response is dominated by a single highly restricted TcR clonotype that selects identical combinations of hypervariable Valpha, Vbeta, D, J, and N region genes. We have determined the 1.5 Angstrom crystal structure of this "public" TcR, revealing that five of the six hypervariable loops adopt novel conformations providing a unique combining site that contains a deep pocket predicted to overlay the HLA B8-peptide complex. The findings suggest a structural basis for the immunodominance of this clonotype in the immune response to EBV.