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T cell-APC conjugation as mediated by leukocyte function-associated antigen-1 (LFA-1)-intercellular adhesion molecule (ICAM)-1 binding is followed by formation of the supramolecular activation cluster (SMAC) at the immunological synapse. The intracellular processes that regulate SMAC formation and its influence on T cell function are important questions to be addressed. Here, using a mutational approach, we demonstrate that binding of adaptor adhesion and degranulation promoting adaptor protein (ADAP) to SLP-76 differentially regulates peripheral SMAC (pSMAC) formation relative to conjugation. Although mutation of the YDDV sites (termed M12) disrupted SLP-76 SH2 domain binding and prevented the ability of ADAP to increase conjugation and LFA-1 clustering, M12 acted selectively as a dominant negative (DN) inhibitor of pSMAC formation, an effect that was paralleled by a DN effect on interleukin-2 production. ADAP also colocalized with LFA-1 at the immunological synapse. Our findings identify ADAP-SLP-76 binding as a signaling event that differentially regulates SMAC formation, and support a role for SMAC formation in T cell cytokine production.

Original publication




Journal article


J exp med

Publication Date





1063 - 1074


Adaptor Proteins, Signal Transducing, Animals, Antigen-Presenting Cells, Binding Sites, Complement Membrane Attack Complex, Complement System Proteins, Glycoproteins, Integrins, Interleukin-2, Lymphocyte Activation, Lymphocyte Function-Associated Antigen-1, Mice, Phosphoproteins, Receptors, Antigen, T-Cell, T-Lymphocytes, src Homology Domains