Tyrosine-phosphorylated T cell receptor ζ chain associates with the actin cytoskeleton upon Activation of mature T lymphocytes

AbstractThe multichain T cell antigen receptor (TCR) is composed of an antigen binding (αβ) domain and associated signal-transducing complexes, the CD3 (γ, σ, and ϵ) and the ζ chains. The ζ chain (TCRζ) plays a key role in signal transduction. We show here that TCR ligation induces association of tyrosine-phosphorylated TCRζ with the detergent-insoluble cell fraction. The microfilament poison, cytochalasin D, disrupts this association and enhances the coprecipitation of actin with TCRζ after receptor ligation. This microfilament association is specific to TCR-associated polypeptides containing at least one intact immunoreceptor tyrosine-based activation motif (ITAM). Mapping studies using transfectants and chimeric TCRζ chain constructs suggest that the third ITAM is necessary and sufficient for association, if the distal tyrosine is intact. This cytoskeletal association is directly correlated with IL-2 production, and ligation of TCR on immature thymocytes does not induce TCRζ-cytoskeleton association. These data thus provide direct evidence of a developmentally regulated activation-dependent interaction between a lymphocyte antigen receptor and the actin cytoskeleton