3hg1

Publication Abstract from PubMed

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.

Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor.,Cole DK, Yuan F, Rizkallah PJ, Miles JJ, Gostick E, Price DA, Gao GF, Jakobsen BK, Sewell AK J Biol Chem. 2009 Oct 2;284(40):27281-9. Epub 2009 Jul 15. PMID:19605354^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.