title: Is the Framework of Cohn's 'Tritope Model' for How T Cell Receptors Recognize Peptide/Self-MHC Complexes and Allo-MHC Plausible?
abstract: Cohn has developed the tritope model to describe how distinct domains of the T cell receptor (TcR) recognize peptide/self-MHC complexes and allo-MHC. He has over the years employed this model as a framework for considering how the TcR might mediate various signals [1-5]. In a recent publication [5], Cohn employs the Tritope Model to propose a detailed mechanism for the T cell receptor's involvement in positive thymic selection [5]. During a review of this proposal, I became uneasy over the plausibility of the underlying framework of the Tritope Model. I outline here the evolutionary considerations making me question this framework. I also suggest that the proposed framework underlying the Tritope Model makes strong predictions whose validity can most probably be assessed by considering observations reported in the literature.
authors.affiliation: Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Peter A
authors.identifier: http://orcid.org/0000-0002-9156-9846
authors.initials: PA
authors.lastname: Bretscher
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002454:Cell Differentiation; D060966:Clonal Selection, Antigen-Mediated; D006649:Histocompatibility Antigens / Q000378:metabolism; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D018448:Models, Immunological; D010455:Peptides / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D006649:Histocompatibility Antigens; D007519:Isoantigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell