THE CD3 CHAINS OF THE T-CELL ANTIGEN RECEPTOR ASSOCIATE WITH THE ZAP-70 TYROSINE KINASE AND ARE TYROSINE-PHOSPHORYLATED AFTER RECEPTOR STIMULATION

Recent work indicates that signaling events resulting from stimulation of the T cell antigen receptor (TCR) can be initiated by the CD3 comp lex (gamma, delta, epsilon) as well as the zeta chains of the receptor . To help characterize the signaling function of CD3 we examined its a ssociated tyrosine kinase activity since induction of tyrosine phospho rylation is one of the earliest signaling events. Our results indicate that at least two kinases, lck and ZAP-70, contribute to the CD3-asso ciated kinase activity. A likely target of this activity is the CD3 co mplex itself since we observed that TCR stimulation resulted in rapid tyrosine phosphorylation of the CD3epsilon and delta chains. To examin e the function of the CD3epsilon chain in particular, we constructed a chimera that fused the extracellular and transmembrane domains of CD8 to the cytoplasmic domain of CD3epsilon. This chimera demonstrated th at CD3epsilon was independently capable of associating with proteins h aving tyrosine kinase activity, including ZAP-70. Our results show tha t the kinase activity that associates with the CD3 complex has charact eristics that are quite similar to the previously characterized zeta-a ssociated kinase activity. This finding suggests that both these compo nents of the TCR initiate signaling events using a common mechanism. H owever, differences in their signaling function could result from reco gnition of distinct substrates.