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

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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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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