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), several receptor ligand pairs, including the T cell receptor (TCR)/major histocompatibility complex (MHC), accumulate at the T cell/APC interface in defined geometrical patterns. This accumulation depends on a movement of the...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2000-08, Vol.97 (18), p.10150-10155
Hauptverfasser: Wülfing, C, Bauch, A, Crabtree, G R, Davis, M M
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Sprache:eng
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Zusammenfassung:During the interaction of a T cell with an antigen-presenting cell (APC), several receptor ligand pairs, including the T cell receptor (TCR)/major histocompatibility complex (MHC), accumulate at the T cell/APC interface in defined 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 actin 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 essential regulator of cytoskeletal rearrangements during T cell activation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.97.18.10150