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.