Germ Line-governed Recognition of a Cancer Epitope by an Immunodominant Human T-cell Receptor
Copyright policy )Germ Line-governed Recognition of a Cancer Epitope by an Immunodominant Human T-cell Receptor
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.
- University of Queensland Australia
- University of Queensland Australia
- Northamptonshire Healthcare NHS Foundation Trust United Kingdom
- University of Oxford United Kingdom
- James Cook University Australia
Models, Molecular, 570, 1303 Biochemistry, Protein Conformation, Receptors, Antigen, T-Cell, CD8-Positive T-Lymphocytes, Peptide vaccines, Substrate Specificity, 1307 Cell Biology, MART-1 Antigen, Antigens, Neoplasm, HLA-A2 Antigen, 1312 Molecular Biology, Humans, Amino Acid Sequence, Melanoma, HLA-A Antigens, Melanoma Patients, Immunodominant Epitopes, Complex Class-i, Structural Basis, Immunity, Innate, Neoplasm Proteins, Germ Cells, Solubility, Thermodynamics
Models, Molecular, 570, 1303 Biochemistry, Protein Conformation, Receptors, Antigen, T-Cell, CD8-Positive T-Lymphocytes, Peptide vaccines, Substrate Specificity, 1307 Cell Biology, MART-1 Antigen, Antigens, Neoplasm, HLA-A2 Antigen, 1312 Molecular Biology, Humans, Amino Acid Sequence, Melanoma, HLA-A Antigens, Melanoma Patients, Immunodominant Epitopes, Complex Class-i, Structural Basis, Immunity, Innate, Neoplasm Proteins, Germ Cells, Solubility, Thermodynamics
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