title: Phenotypic models of T cell activation.
abstract: T cell activation is a crucial checkpoint in adaptive immunity, and this activation depends on the binding parameters that govern the interactions between T cell receptors (TCRs) and peptide-MHC complexes (pMHC complexes). Despite extensive experimental studies, the relationship between the TCR-pMHC binding parameters and T cell activation remains controversial. To make sense of conflicting experimental data, a variety of verbal and mathematical models have been proposed. However, it is currently unclear which model or models are consistent or inconsistent with experimental data. A key problem is that a direct comparison between the models has not been carried out, in part because they have been formulated in different frameworks. For this Analysis article, we reformulated published models of T cell activation into phenotypic models, which allowed us to directly compare them. We find that a kinetic proofreading model that is modified to include limited signalling is consistent with the majority of published data. This model makes the intriguing prediction that the stimulation hierarchy of two different pMHC complexes (or two different TCRs that are specific for the same pMHC complex) may reverse at different pMHC concentrations.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, Oxfordshire OX1 3RE, UK.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lever
authors.affiliation: Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, Oxfordshire OX2 6GG, UK.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Maini
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, Oxfordshire OX1 3RE, UK.
authors.forename: P Anton
authors.initials: PA
authors.lastname: van der Merwe
authors.affiliation: 1] Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, Oxfordshire OX1 3RE, UK. [2] Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, Oxfordshire OX2 6GG, UK.
authors.forename: Omer
authors.initials: O
authors.lastname: Dushek
mesh_terms: D056704:Adaptive Immunity; D000938:Antigen-Presenting Cells / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D018448:Models, Immunological; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell