TCR, LFA-1, and CD28 play unique and complementary roles in signaling T cell cytoskeletal reorganization

T cells interacting with APCs undergo rearrangement of surface receptors an d cytoskeletal elements to face the zone of contact with the APC, This pola rization process is thought to affect T cell signaling by organizing a spec ialized domain on the T cell surface and to direct T cell effector function toward the appropriate APC, We have investigated the contribution of TCR, CD28, and LFA-1 signaling to T cell cytoskeletal polarization by assaying t he response of an Ag-specific Th1 clone toward a panel of transfected APCs expressing MBC class II alone or in combination with ICAM-1 or B7-1, We sho w that polarization of talin, an actin-binding protein, occurs in response to integrin engagement. In contrast, reorientation of the T cell microtubul e-organizing center (MTOC) is dependent on and directed toward the site of TCR signaling, regardless of whether integrins or costimulatory molecules a re engaged. MTOC reorientation in response to peptide-MHC complexes is sens itive to the phosphatidylinositol 3-kinase inhibitor wortmannin, CD28 coeng agement overcomes this sensitivity, as does activation via Ab cross-linking of the TCR or via covalent peptide-MBC complexes, suggesting that phosphat idylinositol 3-kinase is not required per se but rather plays a role in sig nal amplification. Engagement of TCR in trails with LFA-1 results in separa tion of MTOC reorientation and cortical cytoskeletal polarization events, i ndicating that the two processes are not directly mechanistically linked, T hese studies show that T cells mobilize individual cytoskeletal components in response to distinct and specific cell surface interactions.