title: Understanding the complexity and malleability of T-cell recognition.
abstract: T cells are the master regulators of immune system function, continually walking the biological tightrope between adequate host defence and accidental host pathology. Tolerance is maintained or broken through an intricate structural interplay between the T-cell receptor (TCR) and major histocompatibility complex (MHC) molecule cradling peptide antigens (p). Recent advances in structural biology have shown that the TCR/pMHC interface is surprising precise and extraordinarily malleable. We have seen that seemingly minor changes in the TCR/pMHC interface can abrogate function, as well as substantial conformational changes before and after TCR docking. Our understanding of T-cell biology has also been altered with the knowledge that MHC molecules can bind not only peptides, but also an array of natural and synthetic compounds. Here, we review some examples of the precision and flexibility intrinsic to the TCR/p/MHCI axis.
authors.affiliation: 1] QIMR Berghofer Medical Research Institute and QIMR Berghofer Centre for Immunotherapy and Vaccine Development, Brisbane, Queensland, Australia [2] School of Medicine, The University of Queensland, Brisbane, Queensland, Australia [3] Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, UK.
authors.forename: John J
authors.initials: JJ
authors.lastname: Miles
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.affiliation: 1] Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, UK [2] Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia [3] ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: 1] Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia [2] ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell