Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapse.
Activation of T lineage cells through the TCR by peptide-MHC complexes on APC is critically dependent on rearrangement of the actin cytoskeleton. Vav1 is a guanine nucleotide exchange factor for members of the Rho/Rac family of GTPases which is activated following TCR stimulation, suggesting that it may transduce TCR signals to the activation of some or all actin-controlled processes. We show that Vav1-deficient double-positive thymocytes are less efficient at forming conjugates with APC presenting agonist peptide than wild-type cells are. Furthermore we demonstrate that Vav1 is required for TCR-induced activation of the integrin LFA-1, which is likely to explain the defect in conjugate formation. However, once Vav1-deficient cells form a conjugate, the assembly of proteins into an immunological synapse at the conjugate interface is normal. In contrast, thymocyte polarization is defective in the absence of Vav1, as judged by the relocalization of the microtubule-organizing center. These data demonstrate that Vav1 transduces signals to only a subset of cytoskeleton-dependent events at the immunological synapse.
Ardouin
Laurence
L
National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, Great Britain.
Bracke
Madelon
M
Mathiot
Anne
A
Pagakis
Stamatis N
SN
Norton
Trisha
T
Hogg
Nancy
N
Tybulewicz
Victor L J
VL
D000938:Antigen-Presenting Cells / Q000502:physiology; D018797:Cell Cycle Proteins; D016764:Cell Polarity; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000276:immunology*; D020764:cdc42 GTP-Binding Protein / Q000502:physiology
D018797:Cell Cycle Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C496618:VAV1 protein, human; D020764:cdc42 GTP-Binding Protein