title: Potent T cell agonism mediated by a very rapid TCR/pMHC interaction.
abstract: The interaction between T cell receptors (TCR) and peptide-major histocompatibility complex (pMHC) antigens can lead to varying degrees of agonism (T cell activation), or antagonism. The P14 TCR recognises the lymphocytic choriomeningitis virus (LCMV)-derived peptide, gp33 residues 33-41 (KAVYNFATC), presented in the context of H-2D(b). The cellular responses to various related H-2D(b) peptide ligands are very well characterised, and P14 TCR-transgenic mice have been used extensively in models of virus infection, autoimmunity and tumour rejection. Here, we analyse the binding of the P14 soluble TCR to a broad panel of related H-2D(b)-peptide complexes by surface plasmon resonance, and compare this with their diverse cellular responses. P14 TCR binds H-2D(b)-gp33 with a KD of 3 microM (+/-0.5 microM), typical of an immunodominant antiviral TCR, but with unusually fast kinetics (k(off) = 1 s(-1)), corresponding to a half-life of 0.7 s at 25 degrees C, outside the range previously observed for murine agonist TCR/pMHC interactions. The most striking feature of these data is that a very short half-life does not preclude the ability of a TCR/pMHC interaction to induce antiviral immunity, autoimmune disease and tumour rejection.
authors.affiliation: Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, UK. boulterjm@cf.ac.uk
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Boulter
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitz
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Sewell
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Godkin
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: Awen M
authors.initials: AM
authors.lastname: Gallimore
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology; D006183:H-2 Antigens / Q000378:metabolism* / Q000502:physiology; D064532:Histocompatibility Antigen H-2D; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism / Q000502:physiology
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008024:Ligands; D010446:Peptide Fragments; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus