The interaction of CD4 with CD3/Ti regulates tyrosine phosphorylation of substrates during T cell activation.
Phosphorylation of proteins on tyrosine residues during activation was studied in CD3+ CEM T cells. Crosslinking of either CD4 alone or CD3/Ti alone induced weak and transient responses, but the patterns of induced tyrosine-phosphorylated proteins were different. A synergistic but still transient response occurred by the specific interaction of CD4 with CD3/Ti, whereas simultaneous but separate ligation of CD3/Ti and CD4 decreased rather than increased tyrosine phosphorylation of proteins in comparison to CD3/Ti stimulation alone. Stimulation of T cells with immobilized anti-CD3 induced strong and prolonged tyrosine phosphorylation of distinct substrates. CD4 therefore regulates protein tyrosine kinase activation by specific interaction with CD3/Ti, whereas immobilized anti-CD3 may differ from anti-CD3 in solution in the activation of protein tyrosine phosphatase(s) such as CD45.
Ledbetter
J A
JA
Oncogen Corporation, Seattle, WA 98121.
Gilliland
L K
LK
Schieven
G L
GL
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D015704:CD4 Antigens / Q000276:immunology*; D002118:Calcium / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D010449:Peptide Mapping; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D002118:Calcium