title: The structural bases of direct T-cell allorecognition: implications for T-cell-mediated transplant rejection.
abstract: αβ T-cell receptors (TCRs), which can engage a broad array of foreign peptide-laden major histocompatibility complex (pMHC) landscapes, have an essential role in protective immunity. TCRs are selected by pMHC molecules in the thymus and in the periphery, and so are restricted to recognizing 'self'-major histocompatibility complex (MHC) molecules. Accordingly, T cells are inherently cross-reactive, and although the versatility and specificity of this MHC-restricted response are the hallmarks of adaptive immunity, 'unwanted' TCR interactions, such as those observed in T-cell alloreactivity, often occur. Recent data have shown that direct T-cell alloreactivity can arise from peptide-dependent molecular mimicry, as well as distinct pMHC-binding modes. Here we review recent advances in the field, focusing on structural data pertaining to alloreactivity, and discuss the implications for T-cell-mediated transplant rejection.
authors.affiliation: The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Chen
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D008958:Models, Molecular; D018716:Molecular Mimicry / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell