PMID- 19605354 OWN - NLM STAT- MEDLINE DCOM- 20091021 LR - 20240425 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 284 IP - 40 DP - 2009 Oct 2 TI - Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor. PG - 27281-9 LID - 10.1074/jbc.M109.022509 [doi] AB - 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. FAU - Cole, David K AU - Cole DK AD - Department of Infection, Immunity, and Biochemistry, Henry Wellcome Building, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom. FAU - Yuan, Fang AU - Yuan F FAU - Rizkallah, Pierre J AU - Rizkallah PJ FAU - Miles, John J AU - Miles JJ FAU - Gostick, Emma AU - Gostick E FAU - Price, David A AU - Price DA FAU - Gao, George F AU - Gao GF FAU - Jakobsen, Bent K AU - Jakobsen BK FAU - Sewell, Andrew K AU - Sewell AK LA - eng SI - PDB/3HG1 GR - BB/H001085/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090715 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Antigens, Neoplasm) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A*02:01 antigen) RN - 0 (HLA-A2 Antigen) RN - 0 (Immunodominant Epitopes) RN - 0 (MART-1 Antigen) RN - 0 (MLANA protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - Amino Acid Sequence MH - Antigens, Neoplasm/chemistry MH - CD8-Positive T-Lymphocytes/immunology MH - Germ Cells/*immunology MH - HLA-A Antigens/immunology MH - HLA-A2 Antigen MH - Humans MH - Immunity, Innate MH - Immunodominant Epitopes/chemistry/*immunology MH - MART-1 Antigen MH - Melanoma/*immunology MH - Models, Molecular MH - Neoplasm Proteins/chemistry MH - Protein Conformation MH - Receptors, Antigen, T-Cell/chemistry/genetics/*immunology MH - Solubility MH - Substrate Specificity MH - Thermodynamics PMC - PMC2785656 EDAT- 2009/07/17 09:00 MHDA- 2009/10/22 06:00 PMCR- 2010/10/02 CRDT- 2009/07/17 09:00 PHST- 2009/07/17 09:00 [entrez] PHST- 2009/07/17 09:00 [pubmed] PHST- 2009/10/22 06:00 [medline] PHST- 2010/10/02 00:00 [pmc-release] AID - S0021-9258(20)38397-6 [pii] AID - M109.022509 [pii] AID - 10.1074/jbc.M109.022509 [doi] PST - ppublish SO - J Biol Chem. 2009 Oct 2;284(40):27281-9. doi: 10.1074/jbc.M109.022509. Epub 2009 Jul 15.