title: The 1.5 A crystal structure of a highly selected antiviral T cell receptor provides evidence for a structural basis of immunodominance.
abstract: Despite a potential repertoire of >10(15) alphabeta T cell receptors (TcR), the HLA B8-restricted cytolytic T cell response to a latent antigen of Epstein-Barr virus (EBV) is strikingly limited in the TcR sequences that are selected. Even in unrelated individuals this response is dominated by a single highly restricted TcR clonotype that selects identical combinations of hypervariable Valpha, Vbeta, D, J, and N region genes. We have determined the 1.5 A crystal structure of this "public" TcR, revealing that five of the six hypervariable loops adopt novel conformations providing a unique combining site that contains a deep pocket predicted to overlay the HLA B8-peptide complex. The findings suggest a structural basis for the immunodominance of this clonotype in the immune response to EBV.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Craig S
authors.initials: CS
authors.lastname: Clements
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D008024:Ligands; D011948:Receptors, Antigen, T-Cell