A structural basis for immunodominant human T cell receptor recognition
A structural basis for immunodominant human T cell receptor recognition
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DOI：
10.1038/ni942
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发表时间：
2003-07-01
影响因子：
30.5
通讯作者：
Jones, EY
中科院分区：
文献类型：
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作者：
Stewart-Jones, GBE;McMichael, AJ;Jones, EY
hla - a2阳性成人的抗流感CD8(+) T细胞反应几乎完全针对病毒基质蛋白的58-66残基（MP(58-66)）。V(β)17V(α)10.2 T细胞受体（TCRs）在V- β片段的互补决定区3 （CDR3）中含有保守的精氨酸-丝氨酸-丝氨酸序列，主导了这种反应。为了研究远交种群体中免疫优势选择的分子基础，我们在1.4埃的分辨率下测定了V(beta)17V(alpha)10.2与MP(58-66)-HLA-A2复合物的晶体结构。我们表明，虽然TCR通常适合于肽的暴露侧链，但在这种结构中，MP（58-66）只暴露主链原子。V(beta)17V(alpha)10.2的这种独特取向几乎与HLA-A2的肽结合槽正交，有助于V-beta CDR3中的保守精氨酸插入MP(58-66)-HLA-A2表面的缺口中。这种以前未知的结合模式是免疫显性T细胞反应的基础。
The anti-influenza CD8(+) T cell response in HLA-A2-positive adults is almost exclusively directed at residues 58-66 of the virus matrix protein (MP(58-66)). V(beta)17V(alpha)10.2 T cell receptors (TCRs) containing a conserved arginine-serine-serine sequence in complementarity determining region 3 (CDR3) of the V-beta segment dominate this response. To investigate the molecular basis of immunodominant selection in an outbred population, we have determined the crystal structure of V(beta)17V(alpha)10.2 in complex with MP(58-66)-HLA-A2 at a resolution of 1.4 Angstrom. We show that, whereas the TCR typically fits over an exposed side chain of the peptide, in this structure MP(58-66) exposes only main chain atoms. This distinctive orientation of V(beta)17V(alpha)10.2, which is almost orthogonal to the peptide-binding groove of HLA-A2, facilitates insertion of the conserved arginine in V-beta CDR3 into a notch in the surface of MP(58-66)-HLA-A2. This previously unknown binding mode underlies the immunodominant T cell response.