ZAP-70 IS CONSTITUTIVELY ASSOCIATED WITH TYROSINE-PHOSPHORYLATED TCR-ZETA IN MURINE THYMOCYTES AND LYMPH-NODE T-CELLS

Studies with T cell lines and clones have shown that engagement of the TCR results in the tyrosine phosphorylation of the TCR subunits. This leads to the recruitment of the ZAP-70 protein tyrosine kinase, an in teraction involving the two SH2-domains of ZAP-70 with tyrosine-phosph orylated zeta and CD3. However, as previously described, murine thymoc ytes and lymph node T cells express a constitutively tyrosine-phosphor ylated zeta subunit in the basal state. Here, we show that a fraction of ZAP-70 molecules are constitutively associated with tyrosine-phosph orylated zeta. TCR ligation promotes a large increase in the tyrosine phosphorylation of ZAP-70 as well as other TCR subunits. Genetic studi es reveal that the constitutive ZAP-70 association with tyrosine-phosp horylated zeta does not absolutely require either TCR or coreceptor in teractions with MHC molecules.