Inhibition of thymocyte negative selection by T cell receptor antagonist peptides

European Journal of Immunology
O WilliamsD Kioussis

Abstract

The T cell receptor (TCR) recognizes antigenic peptide presented by major histocompatibility complex (MHC) molecules. Analogs of antigenic peptides have been shown to inhibit antigen-specific T cell responses, a phenomenon described as TCR antagonism. We have examined the effect of a natural variant of an antigenic peptide and a synthetic peptide analog, on the responses of mature T cells and immature thymocytes from an alpha-beta TCR-transgenic mouse (F5), the TCR of which recognizes a nonamer peptide from the nucleoprotein (NP) of influenza virus in the context of the H-2Db MHC molecule. Both peptides were shown to antagonize specifically the T cells cytolytic response without being able directly to stimulate mature T cells from these transgenic mice. Furthermore, a negative selection assay in vitro was used to demonstrate for the first time that antagonistic peptides are capable of antagonizing thymocyte deletion induced by antigenic peptides. These data suggest that the final selection of a T cell could be the result of a balance between the positive and negative influences of endogenous peptide ligands.

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Citations

Jun 14, 2005·Cellular Immunology·Stanislav Vukmanović, Fabio R Santori
Mar 1, 1997·Immunology Today·O WilliamsD Kioussis
Apr 1, 1997·Current Opinion in Immunology·P Marrack, J Kappler
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Jun 6, 2000·The Journal of Experimental Medicine·G E PriceD Moskophidis
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May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·O WilliamsD Kioussis
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·C N LeveltS Tonegawa
Apr 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Christophe ViretCharles A Janeway
Aug 28, 2002·Immunity·Fabio R SantoriStephen C Jameson
Jan 13, 2009·Molecular Immunology·Rachel E ShrimptonMary A Ritter
Feb 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jose FaroAntonio Bandeira
Feb 29, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·U BommhardtT Hünig
Sep 15, 2004·The Journal of Biological Chemistry·Jean G SathishR James Matthews

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