3HG1

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

Summary for 3HG1

• Entry DOI: 10.2210/pdb3hg1/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, CANCER/MART-1, ... (8 entities in total)
• Functional Keywords: t-cell receptor, cdr3, phage display, melan-1, mart-1, immune system, disulfide bond, transmembrane, disease mutation, glycation, glycoprotein, immune response, immunoglobulin domain, mhc i, pyrrolidone carboxylic acid, secreted
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P61769
• Total number of polymer chains: 5
• Total formula weight: 93827.93

Authors

Cole, D.K.,Yuan, F.,Rizkallah, P.J.,Miles, J.J.,Gostick, E.,Price, D.A.,Gao, G.F.,Jakobsen, B.K.,Sewell, A.K. (deposition date: 2009-05-13, release date: 2009-07-28, Last modification date: 2014-04-09)

Primary citation

Cole, D.K.,Yuan, F.,Rizkallah, P.J.,Miles, J.J.,Gostick, E.,Price, D.A.,Gao, G.F.,Jakobsen, B.K.,Sewell, A.K.
Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor.
J.Biol.Chem., 284:27281-27289, 2009

PubMed 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.

PubMed: 19605354
DOI: 10.1074/jbc.M109.022509

Experimental method

X-RAY DIFFRACTION (3 Å)