Germ Line-governed Recognition of a Cancer Epitope by an Immunodominant Human T-cell Receptor

被引：125

作者：

Cole, David K. ^{[1
]}

Yuan, Fang ^{[2
]}

Rizkallah, Pierre J. ^{[1
,3
]}

Miles, John J. ^{[1
,4
]}

Gostick, Emma ^{[1
]}

Price, David A. ^{[1
]}

Gao, George F. ^{[5
]}

Jakobsen, Bent K. ^{[6
]}

Sewell, Andrew K. ^{[1
]}

机构：

[1] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff CF14 4XN, S Glam, Wales

[2] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England

[3] STFC Daresbury Lab, Warrington WA4 4AD, Cheshire, England

[4] Univ Queensland, Queensland Inst Med Res, Cellular Immunol Lab, Brisbane, Qld 4029, Australia

[5] Chinese Acad Sci, Inst Microbiol, Beijing 100101, Peoples R China

[6] Immunocore Ltd, Abingdon OX14 4RX, Oxon, England

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 40期

基金：

英国生物技术与生命科学研究理事会;

关键词：

COMPLEX CLASS-I; TUMOR-REACTIVE CTL; PEPTIDE VACCINES; STRUCTURAL BASIS; ANTIGEN; ALPHA; IMMUNOGENICITY; AFFINITY; CHAIN; USAGE;

D O I：

10.1074/jbc.M109.022509

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：27281 / 27289

页数：9

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