Journal of Experimental Medicine, Vol 179, 1973-1983, Copyright © 1994 by Rockefeller University Press

ARTICLES

CD4-mediated enhancement or inhibition of T cell activation does not require the CD4:p56lck association

AC Zerbib, AB Reske-Kunz, P Lock and RP Sekaly
Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montreal, Canada.

CD4 is the coreceptor molecule expressed on the surface of T cells specific for or restricted by class II molecules of the major histocompatibility complex (MHC). Its expression on T cells is required for an optimal response to antigen (Ag). Three mechanisms have been invoked for the involvement of CD4 in T cell activation. First, it was shown that CD4 binds to MHC class II molecules on antigen presenting cells (APCs) thereby favoring an adhesion between effector cells and APCs. Association of CD4 to the T cell receptor and to the tyrosine kinase p56lck have also been shown to be critically involved in the positive function of CD4. Here, we demonstrate that the interaction of CD4 with p56lck is not required to enhance the response of two CD4- dependent, Ag-specific T cell hybridomas. Mutant forms of CD4 (TCD4), which lose association to p56lck, were expressed in these T cells and were shown to enhance the Ag-specific response as efficiently as the wild-type CD4. Moreover both CD4-dependent and independent T cell responses were inhibited by CD4-specific mAbs even when CD4 was not associated with p56lck. These results indicate that mechanisms distinct from sequestration of p56lck and/or negative signaling operate in these inhibitions. Results demonstrating enhancement of TCR-mediated signaling by the coaggregation of TCD4 mutant to the TCR further confirm that the association of p56lck to CD4 is not absolutely required for the regulatory functions of CD4. Our results suggest that the mechanisms implicated in the enhancement of T cell stimulation via CD4 depend solely on the extracellular and transmembrane domains of CD4.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• NAMAZI, M. R. (2003). Pyridoxal 5'-phosphate as a novel weapon against autoimmunity and transplant rejection. FASEB J. 17: 2184-2186 [Abstract] [Full Text]  
• Harding, S., Lipp, P., Alexander, D. R. (2002). A Therapeutic CD4 Monoclonal Antibody Inhibits TCR-{zeta} Chain Phosphorylation, {zeta}-Associated Protein of 70-kDa Tyr319 Phosphorylation, and TCR Internalization in Primary Human T Cells. J. Immunol. 169: 230-238 [Abstract] [Full Text]  
• Thebault, S., Gachon, F., Lemasson, I., Devaux, C., Mesnard, J.-M. (2000). Molecular Cloning of a Novel Human I-mfa Domain-containing Protein That Differently Regulates Human T-cell Leukemia Virus Type I and HIV-1 Expression. J. Biol. Chem. 275: 4848-4857 [Abstract] [Full Text]  
• Bonnard, M., Haughn, L., Julius, M. (1999). CD4-Mediated Inhibiton of IL-2 Production in Activated T Cells. J. Immunol. 162: 1252-1260 [Abstract] [Full Text]  
• Vignali, D. A. A., Vignali, K. M. (1999). Profound Enhancement of T Cell Activation Mediated by the Interaction Between the TCR and the D3 Domain of CD4. J. Immunol. 162: 1431-1439 [Abstract] [Full Text]  
• Gratton, S., Julius, M., Sekaly, R.-P. (1998). lck-Independent Inhibition of T Cell Antigen Response by the HIV gp120. J. Immunol. 161: 3551-3556 [Abstract] [Full Text]  
• Briant, L., Robert-Hebmann, V., Acquaviva, C., Pelchen-Matthews, A., Marsh, M., Devaux, C. (1998). The Protein Tyrosine Kinase p56lck Is Required for Triggering NF-kappa B Activation upon Interaction of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein gp120 with Cell Surface CD4. J. Virol. 72: 6207-6214 [Abstract] [Full Text]  
• Friedman, T. M., Reddy, A. P., Wassell, R., Jameson, B. A., Korngold, R. (1996). Identification of a Human CD4-CDR3-like Surface Involved in CD4+ T Cell Function. J. Biol. Chem. 271: 22635-22640 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS