title: Specificity on a knife-edge: the alphabeta T cell receptor.
abstract: The interaction between the alphabeta T cell receptor (TCR) and the peptide bound to the major histocompatibility complex class I molecule (pMHC-I) constitutes a central interaction in adaptive immunity. How these receptors interact with such low affinity while maintaining exquisite specificity for peptide antigen and host MHC (MHC-I restriction) remains a challenge to be explained by structural immunologists. Moreover, how this extracellular interaction is transmitted as an intracellular signal via the CD3 complex remains unresolved. Nevertheless, several structures of TCRs, non-liganded and ligated to a defined pMHC-I, combined with detailed biophysical analyses, have provided insight of the structural basis of MHC-I restriction. In addition, structures of isolated CD3 components have enabled T cell signalling mechanisms to be postulated. Recent findings in this area, which include seven distinct TCR/pMHC-I complexes, have fundamental implications in adaptive immunity as well as therapeutic applications to modulate the adaptive immune response.
authors.affiliation: The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria 3800, Australia.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Clements
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Dunstone
authors.forename: Whitney A
authors.initials: WA
authors.lastname: Macdonald
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
mesh_terms: D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018448:Models, Immunological; D008958:Models, Molecular; D046912:Multiprotein Complexes; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D046912:Multiprotein Complexes; D016693:Receptors, Antigen, T-Cell, alpha-beta