Abstract
The adaptor protein, LAD/TSAd, plays essential roles in T cell activation. To further understand the functions of this protein, we performed yeast two-hybrid screening using TSAd as bait and identified 67 kDa laminin binding protein (LBP) as the interacting partner. Subsequently, TSAd-LBP interaction was confirmed in D1.1 T cell line. Upon costimulation by T cell receptor (TCR) plus laminin crosslinking or TCR plus integrin alpha6 crosslinking, LBP was coimmunoprecipitated with TSAd. Moreover, TCR plus laminin costimulation-dependent T cell migration was enhanced in D1.1 T cells overexpressing TSAd but was disrupted in D1.1 cells overexpressing dominant negative form of TSAd or TSAd shRNA. These data show that, upon TCR plus integrin costimulation, TSAd associates with LBP and mediates T lymphocyte migration.
Highlights
T cell trafficking is a critical element of cell-mediated immune responses
Among the T cell-specific adaptor protein (TSAd) mutants tested, point mutants of the proline-rich motif (P262A) and the SH2 domain (R141K) displayed reduced and no binding to laminin binding protein (LBP), respectively (Figure 1A). These results indicate that the region encompassing SH2 and proline-rich motif is involved in binding to LBP
We present a novel function of TSAd and LBP in regulating the motility of T cells
Summary
T cell trafficking is a critical element of cell-mediated immune responses. Combinations of various stimuli, such as chemokines, engagement of antigen receptors and binding of integrins to their ligands, trigger the migration of T cells within lymphatic systems and tissues. Upon T cell activation, TSAd is tyrosine-phosphorylated, associates with p56lck and is redistributed from the cytoplasm to the plasma membrane and plays essential roles in p56lck-mediated T cell activation (Choi et al, 1999). Consistent with this finding, proliferation of TSAd-deficient T cells in response to TCR-mediated activation was significantly impaired. We have found that TSAd associates with LBP in response to TCR + integrin coengagement and mediates laminin-dependent FAK phosphorylation and cell migration
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