Physical association of CD4 and CD45 in primary, resting CD4+ T cells.
CD45 is a family of transmembrane protein tyrosine phosphatases that are essential to T lymphocytes' responses to antigen-receptor stimulation. It is involved in the regulation of Src-family protein tyrosine kinases, Lck and Fyn. The object of this study was to determine how CD45 molecules are directed to such substrates at the antigen-receptor complex upon stimulation of resting T cells. We demonstrate that CD45 is physically associated with CD4 in resting, primary lymph node T cells. Further, CD4-dependent, antigen-mediated activation of primary CD4+ T cells results in disruption of CD4-CD45 complexes, suggesting a role for these complexes in the activation process. Moreover, CD45 coprecipitates with CD4 molecules which are associated with Lck, as well as with those which are not associated with Lck. Consistent with these observations and the role of CD45 in the regulation of Lck function, effects on CD4-associated membrane Lck are demonstrable. Since antigen presentation by MHC class II results in the coaggregation of CD4 with the antigen-receptor complex, the association described in this study provides a physical basis through which CD45 could be included.
Bonnard
M
M
Department of Immunology, University of Toronto, Wellesley Hospital Research Institute, Ontario, Canada.
Maroun
C R
CR
Julius
M
M
D000818:Animals; D017951:Antigen Presentation; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000276:immunology; D066298:In Vitro Techniques; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D015704:CD4 Antigens; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens