title: The nature of molecular recognition by T cells.
abstract: Considerable progress has been made in characterizing four key sets of interactions controlling antigen responsiveness in T cells, involving the following: the T cell antigen receptor, its coreceptors CD4 and CD8, the costimulatory receptors CD28 and CTLA-4, and the accessory molecule CD2. Complementary work has defined the general biophysical properties of interactions between cell surface molecules. Among the major conclusions are that these interactions are structurally heterogeneous, often reflecting clear-cut functional constraints, and that, although they all interact relatively weakly, hierarchical differences in the stabilities of the signaling complexes formed by these molecules may influence the sequence of steps leading to T cell activation. Here we review these developments and highlight the major challenges remaining as the field moves toward formulating quantitative models of T cell recognition.
authors.affiliation: Nuffield Department of Clinical Medicine, Weatherall Institute of Molecular Medicine, The University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. sdavis@molbiol.ox.ac.uk
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Davis
authors.forename: Shinji
authors.initials: S
authors.lastname: Ikemizu
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Evans
authors.forename: Lars
authors.initials: L
authors.lastname: Fugger
authors.forename: Talitha R
authors.initials: TR
authors.lastname: Bakker
authors.forename: P Anton
authors.initials: PA
authors.lastname: van der Merwe
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D018801:CD2 Antigens / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen; D006031:Glycosylation; D018796:Immunoconjugates; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D011485:Protein Binding; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018801:CD2 Antigens; D018106:CD28 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D011948:Receptors, Antigen, T-Cell; D000069594:Abatacept