Signal transduction in T helper cells: CD4 coreceptors exert complex regulatory effects on T cell activation and function.
The immune system provides a highly sophisticated surveillance mechanism to detect diverse antigens and to protect the host organism from invading pathogens and altered cells (e.g., virus-infected and tumor cells). Adaptive immune responses depend on the recognition of antigen by specific antigen receptors that are expressed on the surface of T and B lymphocytes. Helper T cells provide regulatory functions and direct the adaptive immune system to respond appropriately to a particular antigen (i.e., cytotoxic T cell responses against viral infections and tumor cells, humoral responses against extracellular bacteria and parasitic worms). Helper T cells express CD4 coreceptors, which recognize conserved domains on proteins expressed by the class II major histocompatibility complex, the same proteins that present antigen to the T cell receptor. Recent progress in T cell biology has identified multiple regulatory functions of CD4 during thymocyte development and antigen stimulation of mature T helper cells. Signaling pathways induced by engagement of CD4 independently of T cell receptor signaling mediate these regulatory functions. In this review, we discuss the regulation of T cell signaling and emphasize the functional consequences of proper and improper CD4 coreceptor signaling.
König
Rolf
R
Department of Microbiology and Immunology, Sealy Center for Molecular Science, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1070, USA. rokonig@utmb.edu
Zhou
Wenhong
W
D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D008213:Lymphocyte Activation; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II