Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor

Cole, David ORCID: https://orcid.org/0000-0003-0028-9396, Yuan, Fang, Rizkallah, Pierre ORCID: https://orcid.org/0000-0002-9290-0369, Miles, John James, Gostick, Emma, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Gao, George F., Jakobsen, Bent K. and Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135 2009. Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor. Journal of Biological Chemistry 284 (40) , 27281-27289. 10.1074/jbc.M109.022509

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > Q Science (General) R Medicine > RZ Other systems of medicine
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0021-9258
Last Modified:	10 Jun 2023 01:08
URI:	https://orca.cardiff.ac.uk/id/eprint/25250

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