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 α (TCRα) 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 (A2-ELA). 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. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
CITATION STYLE
Cole, D. K., Yuan, F., Rizkallah, P. J., Miles, J. J., Gostick, E., Price, D. A., … Sewell, A. K. (2009). Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor. Journal of Biological Chemistry, 284(40), 27281–27289. https://doi.org/10.1074/jbc.M109.022509
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