The vav exchange factor is an essential regulator in actin-dependent receptor translocation to the lymphocyte-antigen-presenting cell interface

During the interaction of a T cell with an antigen-presenting cell (APC), s everal receptor ligand pairs, including the T cell receptor (TCR)/major his tocompatibility complex (MHC), accumulate at the T cell/APC interface in de fined geometrical patterns. This accumulation depends on a movement of the T cell cortical actin cytoskeleton toward the interface. Here we study the involvement of the guanine nucleotide exchange factor vav in this process. We crossed 129 vav(-/-) mice with B10/BR 5C.C7 TCR transgenic mice and used peptide-loaded APCs to stimulate T cells from the offspring, We found that the accumulation of TCR/MHC at the T cell/APC interface and the T cell act in cytoskeleton rearrangement were clearly defective in these vav(+/-) mice , A comparable defect in superantigen-mediated T cell activation of T cells from non-TCR transgenic 129 mice was also observed, although in this case it was more apparent in vav(-/-) mice, These data indicate that vav is an e ssential regulator of cytoskeletal rearrangements during T cell activation.