TYROSINE-PHOSPHORYLATED T-CELL RECEPTOR ZETA-CHAIN ASSOCIATES WITH THE ACTIN CYTOSKELETON UPON ACTIVATION OF MATURE T-LYMPHOCYTES

The multichain T cell antigen receptor (TCR) is composed of an antigen binding (alpha/beta) domain and associated signal-transducing complex es, the CD3 (gamma, delta, and epsilon) and the zeta chains, The zeta chain (TCR zeta) plays a key role in signal transduction. We show here that TCR ligation induces association of tyrosine-phosphorylated TCR zeta with the detergent-insoluble cell fraction. The microfilament poi son, cytochalasin D, disrupts this association and enhances the coprec ipitation of actin with TCR zeta after receptor ligation. This microfi lament association is specific to TCR-associated polypeptides containi ng at least one intact immunoreceptor tyrosine-based activation motif (ITAM), Mapping studies using transfectants and chimeric TCR zeta chai n constructs suggest that the third ITAM is necessary and sufficient f or association, if the distal tyrosine is intact. This cytoskeletal as sociation is directly correlated with IL-2 production, and ligation of TCR on immature thymocytes does not induce TCR zeta-cytoskeleton asso ciation. These data thus provide direct evidence of a developmentally regulated activation-dependent interaction between a lymphocyte antige n receptor and the actin cytoskeleton.