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

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 alpha (TCRalpha) 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.

SUBMITTER: Cole DK

PROVIDER: S-EPMC2785656 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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

Cole David K DK Yuan Fang F Rizkallah Pierre J PJ Miles John J JJ Gostick Emma E Price David A DA Gao George F GF Jakobsen Bent K BK Sewell Andrew K AK

The Journal of biological chemistry 20090715 40

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 (TCRalpha) 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 pepti ...[more]

PMID: 19605354

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