title: Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate extrinsic factors in guiding MHC restriction.
abstract: The underlying basis of major histocompatibility complex (MHC) restriction is unclear. Nevertheless, current data suggest that a common thermodynamic signature dictates alphabeta T cell receptor (TcR) ligation. To evaluate whether this thermodynamic signature defines MHC restriction, we have examined the thermodynamic basis of a highly characterized immunodominant TcR interacting with its cognate peptide-MHC-I ligand. Surprisingly, we observed this interaction to be governed by favorable enthalpic and entropic forces, which is in contrast to the prevailing generality, namely, enthalpically driven interactions combined with markedly unfavorable entropic forces. We conclude that extrinsic molecular factors, such as coreceptor ligation, conformational adjustments involved in TcR signaling, or constraints dictated by higher-order arrangement of ligated TcRs, might play a greater role in guiding MHC restriction than appreciated previously.
authors.affiliation: Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Ely
authors.forename: Travis
authors.initials: T
authors.lastname: Beddoe
authors.forename: Craig S
authors.initials: CS
authors.lastname: Clements
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Matthews
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
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; D019277:Entropy; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism; D015235:HLA-B Antigens / Q000737:chemistry* / Q000378:metabolism*; D015795:HLA-B8 Antigen; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D046912:Multiprotein Complexes; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D020349:Surface Plasmon Resonance; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013816:Thermodynamics; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D015235:HLA-B Antigens; C509422:HLA-B*08:01 antigen; D015795:HLA-B8 Antigen; D008024:Ligands; D046912:Multiprotein Complexes; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin