Negative regulation of T cell receptor signals

Current Opinion in Pharmacology
Manu Rangachari, Josef M Penninger

Abstract

T cells undergo clonal expansion upon encountering cognate antigen in peripheral lymphoid tissues. They require signals through both the T cell receptor and the costimulatory receptor CD28 for this process to occur. In the absence of CD28 stimulation, T cell receptor signals are repressed by the ubiquitin ligase Cbl-b, which negatively regulates the activity of the downstream effectors PI3Kp85 and Vav1. CD28 signals overcome this repression, at least in part, by ubiquitinating and degrading Cbl-b itself. CD28 signals induce clustering of cell-surface receptors, cell division and optimal interleukin-2 production. The Cbl-b/CD28 regulatory axis has profound implications for pathological conditions ranging from autoimmunity to cancer.

Citations

Jun 5, 2008·Cancer Immunology, Immunotherapy : CII·Cristan M JubalaJaime F Modiano
Sep 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shekhar SrivastavaEdward Y Skolnik
Dec 29, 2009·The Journal of Biological Chemistry·Jung Ha KimNacksung Kim
May 4, 2013·Immunotherapy·Roza NurievaAnupama Sahoo
Mar 20, 2010·Seminars in Immunopathology·Christopher E Rudd
May 29, 2009·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·J-L QuY-P Liu
Mar 26, 2005·Immunological Reviews·Silke Paust, Harvey Cantor
Apr 15, 2011·Immunological Reviews·Roza I NurievaChen Dong
Feb 22, 2007·Journal of Cellular Physiology·Lianjun Zhang, Yong Zhao
Nov 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mohammed ShamimM Suresh
Nov 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maureen A McGargillStephen M Hedrick
Mar 30, 2007·Seminars in Immunology·Stefanie Loeser, Josef M Penninger

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