MULTI-STAGE T CELL-DENDRITIC CELL INTERACTIONS CONTROL OPTIMAL CD4 T CELL ACTIVATION THROUGH THE ADAP-SKAP55 SIGNALING MODULE

摘要

The antigen-specific interactions between T cells and dendritic cells progress through dynamic contact stages in vivo consisting of early long-term stable contacts and later confined, yet motile, short-lived contacts. The signaling pathways that control in vivo interaction dynamics between T cells and dendritic cells during priming remain undefined. ADAP is a multi-functional adapter that regulates “inside-out” signaling from the T cell receptor to integrins. Using two-photon microscopy, we demonstrate that in the absence of ADAP, CD4 T cells make fewer early-stage stable contacts with antigen-laden dendritic cells, and the interactions are characterized by brief repetitive contacts. Furthermore, ADAP-deficient T cells show reduced contacts at the late motile contact phase and display less confinement around dendritic cells. The altered T cell interaction dynamics in the absence of ADAP are associated with defective early proliferation and attenuated T cell receptor signaling in vivo. Regulation of multi-stage contact behaviors and optimal T cell signaling involves the interaction of ADAP with the adapter SKAP55. Thus, integrin activation by the ADAP-SKAP55 signaling module controls the stability and duration of T cell-dendritic cell contacts during the progressive phases necessary for optimal T cell activation.