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J. Cell Biol.,
Volume 140, Number 4, February 23, 1998 861-871
§
* Department of Medicine, Abstract. Binding of a T cell to an appropriate antigen-presenting cell (APC) induces the rapid reorientation
of the T cell cytoskeleton and secretory apparatus towards the cell-cell contact site in a T cell antigen receptor (TCR) and peptide/major histocompatibility complex-dependent process. Such T cell polarization
directs the delivery of cytokines and cytotoxic mediators towards the APC and contributes to the highly selective and specific action of effector T cells. To study
the signaling pathways that regulate cytoskeletal rearrangements in T lymphocytes, we set up a conjugate formation assay using Jurkat T cells as effectors and
cell-sized latex beads coated with various antibodies as
artificial APCs. Here, we report that beads coated with
antibodies specific for the TCR-CD3 complex were sufficient to induce T cell polarization towards the bead
attachment site, as judged by reorientation of the microtubule-organizing center (MTOC) and localized actin polymerization. Thus, these cytoskeletal changes
did not depend on activation of additional coreceptors.
Moreover, single subunits of the TCR complex, namely
TCR- Department of Microbiology and Immunology, § Howard Hughes Medical Institute, University of
California, San Francisco, San Francisco, California 94143
and CD3
, were equally effective in inducing cytoskeletal polarization. However, mutagenesis of the
immunoreceptor tyrosine-based activation motifs
(ITAMs), present three times in TCR- and once in
CD3, revealed that the induction of cytoskeletal rearrangements required the presence of at least one intact
ITAM. In agreement with this result, lack of functional
Lck, the protein tyrosine kinase responsible for ITAM
phosphorylation, abolished both MTOC reorientation
and polarized actin polymerization. Both inhibitor and
transient overexpression studies demonstrated that MTOC reorientation could occur in the absence of Ras
activation. Our results suggest that APC-induced T cell
polarization is a TCR-mediated event that is coupled to
the TCR by the same signaling motif as TCR-induced
gene activation, but diverges in its distal signaling requirements.
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