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Potent T cell agonism mediated by a very rapid TCR/pMHC interaction

Boulter, Jonathan M., Schmitz, Nicole, Sewell, Andrew K. ORCID:, Godkin, Andrew James ORCID:, Bachmann, Martin F. and Gallimore, Awen Myfanwy ORCID: 2007. Potent T cell agonism mediated by a very rapid TCR/pMHC interaction. European Journal of Immunology 37 (3) , pp. 798-806. 10.1002/eji.200636743

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Uncontrolled Keywords: Biophysics; Protein-protein interactions; TCR Animals Antigens, Viral/metabolism Antigens, Viral/physiology Glycoproteins/metabolism Glycoproteins/physiology H-2 Antigens/metabolism* H-2 Antigens/physiology Ligands Lymphocyte Activation/immunology Mice Mice, Transgenic Peptide Fragments/metabolism Peptide Fragments/physiology Peptides/genetics Peptides/metabolism* Peptides/physiology Protein Binding/immunology Receptors, Antigen, T-Cell, alpha-beta/metabolism* Receptors, Antigen, T-Cell, alpha-beta/physiology T-Lymphocytes/immunology* T-Lymphocytes/metabolism* Viral Proteins/metabolism Viral Proteins/physiology
ISSN: 1521-4141
Last Modified: 17 Oct 2022 08:27

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