The CD4/CD8:p56lck complex in T lymphocytes: a potential mechanism to regulate T-cell growth.
The CD4 and CD8 antigens on the surface of T cells appear to bind to major histocompatibility complex (MHC) class II and I antigens, respectively. These receptors have also been found to regulate T cell growth in a manner independent of MHC recognition. In this report, we describe recent work showing that the CD4 and CD8 receptors are coupled to a protein-tyrosine kinase, p56lck, from T lymphocytes. The p56lck protein is a member of the src family, which plays a crucial role in the activation and transformation of various mammalian cells. The CD4/CD8:p56lck complex is catalytically active as shown by its ability to phosphorylate at 55-60 kDa. Two-dimensional, nonequilibrium gel electrophoresis demonstrated the similarity of p56lck associated with the CD4 and CD8 antigens. Detergents were found to vary in their ability to solubilize the CD4:p56lck complex in a catalytically active form. We further demonstrated by in vitro phosphorylation that members of the CD3 complex including the gamma, delta, and epsilon chains, as well as a putative zeta subunit can be phosphorylated at tyrosyl residues by the CD4/CD8:p56lck complex. Thus, this interaction may play an important role in the activation of T cells, and may mediate the cooperative interaction between the CD4/CD8 antigens and the Ti(TcR)/CD3 complex. This interaction also represents a possible precedent by which other members of the src family (c-src, c-yes, c-fgr, etc.) may be found to interact with mammalian growth receptors.
Rudd
C
C
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Helms
S
S
Barber
E K
EK
Schlossman
S F
SF
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology*; D016827:CD8 Antigens; D002384:Catalysis; D002455:Cell Division; D002461:Cell Line, Transformed; D003902:Detergents; D006801:Humans; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D003902:Detergents; D011505:Protein-Tyrosine Kinases