Bowness P, Allen R L, McMichael A J
Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford.
Eur J Immunol. 1994 Oct;24(10):2357-63. doi: 10.1002/eji.1830241015.
The fine specificity of T cell recognition of peptide analogues of the influenza nucleoprotein epitope, NP 383-391 SRYWAIRTR, was studied using HLA B27-restricted influenza-specific cytotoxic T cell (CTL) clones, of defined T cell receptor (TcR) usage, derived from unrelated individuals following natural infection. Even conservative amino acid substitutions of the peptide residues P4, P7 and P8 influenced CTL recognition. These side chains are probably directly contacted by the TcR. CTL clones which used the TcR V alpha 14 gene segment (but not those using TcR V alpha 12) were also sensitive to P1 substitutions, suggesting that the TcR alpha chain of these clones lies over the N terminus of bound peptide, and that the "footprint" of certain TcR can span all exposed residues of a peptide bound to a major histocompatibility complex class I molecule. These results, taken together with previous structural and functional data, suggest that, for nonamer peptides bound to HLA B27, P1, P4 and P8 are "flag" residues with TcR-accessible side chains.
利用 HLA B27 限制性流感特异性细胞毒性 T 细胞（CTL）克隆，对流感核蛋白表位 NP 383 - 391 SRYWAIRTR 的肽类似物的 T 细胞识别精细特异性进行了研究。这些克隆来自自然感染后的无关个体，具有明确的 T 细胞受体（TcR）使用情况。即使肽残基 P4、P7 和 P8 进行保守氨基酸替换也会影响 CTL 识别。这些侧链可能直接与 TcR 接触。使用 TcR Vα14 基因片段的 CTL 克隆（但使用 TcR Vα12 的克隆则不然）对 P1 替换也敏感，这表明这些克隆的 TcR α 链位于结合肽的 N 末端上方，并且某些 TcR 的“足迹”可以跨越与主要组织相容性复合体 I 类分子结合的肽的所有暴露残基。这些结果与先前的结构和功能数据一起表明，对于与 HLA B27 结合的九聚体肽，P1、P4 和 P8 是具有 TcR 可及侧链的“标记”残基。
