Research ArticleImmunology

The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4+ T cells

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Sci. Signal.  10 Jul 2018:
Vol. 11, Issue 538, eaar3083
DOI: 10.1126/scisignal.aar3083

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VAV1, a T cell hub

The guanine nucleotide exchange factor VAV1 is required for T cell receptor (TCR) signaling and activation of T cells. By analyzing the VAV1 interactome, Gaud et al. found that VAV1 also interacted with the costimulatory molecule CD226. Engagement of CD226 activated VAV1, which in turn enhanced the TCR-dependent production of the proinflammatory cytokine IL-17 by human T cells. A variant of CD226 that is associated with autoimmune diseases stimulated more VAV1 activity and IL-17 production than did wild-type CD226, demonstrating that VAV1-mediated cross-talk between the CD226 and TCR signaling pathways affects both normal and pathological T cell activation.