Cole, David K., Yuan, Fang, Rizkallah, Pierre J., Miles, John J., Gostick, Emma, Price, David A., Gao, George F., Jakobsen, Bent K., and Sewell, Andrew K. (2009) Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor. Journal of Biological Chemistry, 284 (40). pp. 27281-27289.

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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 ID:	45385
Item Type:	Article (Research - C1)
ISSN:	1083-351X
Funders:	Cardiff University (CU), Biotechnology and Biological Sciences Research Council (BBSRC), Leverhulme Trust (LT), National Health and Medical Research Council (NHMRC), Medical Research Council (MRC)
Projects and Grants:	BBSRC Grant BB/H001085/1
Date Deposited:	06 Sep 2016 23:07
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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