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ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation

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 i...

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Autores principales: Wang, Hongyan, McCann, Fiona E., Gordan, John D., Wu, Xiang, Raab, Monika, Malik, Talat H., Davis, Daniel M., Rudd, Christopher E.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211848/
https://www.ncbi.nlm.nih.gov/pubmed/15477347
http://dx.doi.org/10.1084/jem.20040780
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author Wang, Hongyan
McCann, Fiona E.
Gordan, John D.
Wu, Xiang
Raab, Monika
Malik, Talat H.
Davis, Daniel M.
Rudd, Christopher E.
author_facet Wang, Hongyan
McCann, Fiona E.
Gordan, John D.
Wu, Xiang
Raab, Monika
Malik, Talat H.
Davis, Daniel M.
Rudd, Christopher E.
author_sort Wang, Hongyan
collection PubMed
description 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.
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spelling pubmed-22118482008-03-11 ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation Wang, Hongyan McCann, Fiona E. Gordan, John D. Wu, Xiang Raab, Monika Malik, Talat H. Davis, Daniel M. Rudd, Christopher E. J Exp Med Article 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. The Rockefeller University Press 2004-10-18 /pmc/articles/PMC2211848/ /pubmed/15477347 http://dx.doi.org/10.1084/jem.20040780 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Wang, Hongyan
McCann, Fiona E.
Gordan, John D.
Wu, Xiang
Raab, Monika
Malik, Talat H.
Davis, Daniel M.
Rudd, Christopher E.
ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation
title ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation
title_full ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation
title_fullStr ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation
title_full_unstemmed ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation
title_short ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation
title_sort adap–slp-76 binding differentially regulates supramolecular activation cluster (smac) formation relative to t cell–apc conjugation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211848/
https://www.ncbi.nlm.nih.gov/pubmed/15477347
http://dx.doi.org/10.1084/jem.20040780
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