Tyrosine phosphorylation and recruitment of ZAP-70 to the CD3-TCR complex are defective after CD2 stimulation

CD2 has been described as an alternative transduction pathway sharing the same biochemical cascade as CD3. The T cell-specific protein tyrosine kinase (PTK) ZAP-70 is believed to play a key role in early tyrosine phosphorylations of cellular proteins induced by CD3 stimulation, We show in the present report that ZAP-70 is insignificantly tyrosine phosphorylated and recruited to CD3 after CD2 stimulation in Jurkat T cells. The same result is obtained for p72(syk), a PTK structurally and functionally related to ZAP-70. Several studies have suggested a model in which p56(lck) would be responsible after CD3 triggering for the phosphorylation of particular tyrosine residues in the immunoreceptor tyrosine-based activation motifs of the CD3 chains, inducing the recruitment and the tyrosine phosphorylation of ZAP-70. In jurkat cells, p56(lck) is required for CD3- or CD2;induced tyrosine phosphorylations and clearly activated after CD2 cross-linking, However, we find that the CD3 complex, and especially its zeta-chain, are faintly tyrosine phosphorylated after CD2 triggering. By contrast, CD2 induces PLC gamma-1 tyrosine phosphorylation as efficiently as CD3, with a correlated inositol phosphate production and intracellular calcium increase,and even a higher production of IL-2. interestingly, the SH2 domains of PLC gamma-1 associate with ZAP-70 upon CD3 stimulation while they bind, in CD2-activated cells, to a heavily tyrosine-phosphorylated 62-kDa protein. Altogether, these findings suggest that CD2 could bypass the PTK ZAP-70 for PLC gamma-1 activation and involves a preferential cascade comprising p56(lck) and a p62 protein, possibly acting as an anchor molecule.