Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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

DOI

10.1084/jem.20040780

Type

Journal article

Journal

J Exp Med

Publication Date

18/10/2004

Volume

200

Pages

1063 - 1074

Keywords

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