CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse

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Item Type:	Article
Title:	CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse
Creators Name:	Li, Q.J., Dinner, A.R., Qi, S., Irvine, D.J., Huppa, J.B., Davis, M.M. and Chakraborty, A.K.
Abstract:	How T cells respond with extraordinary sensitivity to minute amounts of agonist peptide and major histocompatibility complex (pMHC) molecules on the surface of antigen-presenting cells bearing large numbers of endogenous pMHC molecules is not understood. Here we present evidence that CD4 affects the responsiveness of T helper cells by controlling spatial localization of the tyrosine kinase Lck in the synapse. This finding, as well as further in silico and in vitro experiments, led us to develop a molecular model in which endogenous and agonist pMHC molecules act cooperatively to amplify T cell receptor signaling. At the same time, activation due to endogenous pMHC molecules alone is inhibited. A key feature is that the binding of agonist pMHC molecules to the T cell receptor results in CD4-mediated spatial localization of Lck, which in turn enables endogenous pMHC molecules to trigger many T cell receptors. We also discuss broader implications for T cell biology, including thymic selection, diversity of the repertoire of self pMHC molecules and serial triggering.
Keywords:	Antigen-Presenting Cells, Antigens, CD4 Antigens, Computer Simulation, Computer-Assisted Image Processing, Lymphocyte Activation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Major Histocompatibility Complex, Immunological Models, T-Cell Antigen Receptors, Signal Transduction, T-Lymphocytes, Animals, Mice
Source:	Nature Immunology
ISSN:	1529-2908
Publisher:	Nature Publishing Group
Volume:	5
Number:	8
Page Range:	791-9
Date:	1 August 2004
Official Publication:	https://doi.org/10.1038/ni1095
PubMed:	View item in PubMed

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