LIME mediates immunological synapse formation through activation of VAV

Lck Interacting Membrane protein (LIME) was previously characterized as a transmembrane adaptor protein mediating TCR-dependent T cell activation. Here, we show that LIME associates with Vav in response to TCR stimulation and is required for Vav guanine nucleotide exchange factor (GEF) activity for Rac1. Consistent with this finding, actin polymerization at the immunological synapse (IS) was markedly enhanced by overexpression of LIME, but was reduced by expression of a LIME shRNA. Moreover, TCR-mediated cell adhesion to ICAM-1, laminin, or fibronectin was downregulated by expression of LIME shRNA. In addition, in the IS, LIME but not LAT was found to localize at the peripheral-supramolecular activation cluster (p-SMAC) where the integrins were previously shown to be localized. Together, these results establish LIME as a transmembrane adaptor protein linking TCR stimulation to IS formation and integrin activation through activation of Vav.