title: T cell antigen receptor recognition of antigen-presenting molecules.
abstract: The Major Histocompatibility Complex (MHC) locus encodes classical MHC class I and MHC class II molecules and nonclassical MHC-I molecules. The architecture of these molecules is ideally suited to capture and present an array of peptide antigens (Ags). In addition, the CD1 family members and MR1 are MHC class I-like molecules that bind lipid-based Ags and vitamin B precursors, respectively. These Ag-bound molecules are subsequently recognized by T cell antigen receptors (TCRs) expressed on the surface of T lymphocytes. Structural and associated functional studies have been highly informative in providing insight into these interactions, which are crucial to immunity, and how they can lead to aberrant T cell reactivity. Investigators have determined over thirty unique TCR-peptide-MHC-I complex structures and twenty unique TCR-peptide-MHC-II complex structures. These investigations have shown a broad consensus in docking geometry and provided insight into MHC restriction. Structural studies on TCR-mediated recognition of lipid and metabolite Ags have been mostly confined to TCRs from innate-like natural killer T cells and mucosal-associated invariant T cells, respectively. These studies revealed clear differences between TCR-lipid-CD1, TCR-metabolite-MR1, and TCR-peptide-MHC recognition. Accordingly, TCRs show remarkable structural and biological versatility in engaging different classes of Ag that are presented by polymorphic and monomorphic Ag-presenting molecules of the immune system.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia; email: Jamie.rossjohn@monash.edu , Stephanie.Gras@monash.edu.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: John J
authors.initials: JJ
authors.lastname: Miles
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D003429:Cross Reactions / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D008055:Lipids / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008055:Lipids; D011948:Receptors, Antigen, T-Cell
keywords: CD1; MR1; T cell antigen receptor; major histocompatibility complex