Germ Line-governed Recognition of a Cancer Epitope by an Immunodominant Human T-cell Receptor
Germ Line-governed Recognition of a Cancer Epitope by an Immunodominant Human T-cell Receptor
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DOI：
10.1074/jbc.m109.022509
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发表时间：
2009-10-02
影响因子：
4.8
通讯作者：
Sewell, Andrew K.
中科院分区：
文献类型：
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作者：
Cole, David K.;Yuan, Fang;Sewell, Andrew K.
对MART-1-（26-35）（一种受人白细胞抗原（HLA）A* 0201限制的显性黑色素瘤表位）具有特异性的CD 8（+）T细胞在初始T细胞库中异常常见。值得注意的是，TRAV 12 -2基因用于在> 87%的这些T细胞中编码T细胞受体α（TCR α）链。在这里，这种遗传偏好的分子基础是从与临床相关的异型肽ELAGIGILTV复合的原型TRAV 12 -2编码的TCR的结构和热力学性质揭示的，所述异型肽ELAGIGILTV与HLA-A*0201（A2 ELA）结合。不寻常的是，TCR的TRAV 12 -2种系编码区在TCR/A2-ELA界面处主导与肽的主要原子接触。这种抗原识别的“先天”模式可能解释了CD 8（+）T细胞对该表位的独特特征和异常频率。
CD8(+) T-cells specific for MART-1-(26-35), a dominant melanoma epitope restricted by human leukocyte antigen (HLA)A* 0201, are exceptionally common in the naive T-cell repertoire. Remarkably, the TRAV12-2 gene is used to encode the T-cell receptor alpha(TCR alpha) chain in > 87% of these T-cells. Here, the molecular basis for this genetic bias is revealed from the structural and thermodynamic properties of an archetypal TRAV12-2-encoded TCR complexed to the clinically relevant heteroclitic peptide, ELAGIGILTV, bound to HLA-A*0201 (A2ELA). Unusually, the TRAV12-2 germ line-encoded regions of the TCR dominate the major atomic contacts with the peptide at the TCR/A2-ELA interface. This "innate" pattern of antigen recognition probably explains the unique characteristics and extraordinary frequencies of CD8(+) T-cell responses to this epitope.