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Adhesion- and degranulation-promoting adapter protein is required for efficient thymocyte development and selection.

Jennifer N Wu·Shereen Gheith·Natalie A Bezman·Qing-Hua Liu·Lindsey V Fostel·Andrew M Swanson·Bruce D Freedman·Gary A Koretzky·Erik J Peterson
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Abstract

Adhesion- and degranulation-promoting adapter protein (ADAP) is required in TCR-induced activation and proliferation of peripheral T cells. Loss of ADAP also impairs TCR-initiated inside-out activation of the integrin LFA-1 (CD11a/CD18, alphaLbeta2). In this study, we demonstrate that ADAP-deficient CD4/CD8 double-positive (DP) cells have a diminished ability to proliferate, and that these DP thymocytes up-regulate CD69 poorly in vivo. Moreover, in both MHC class I- and class II-restricted TCR transgenic models, loss of ADAP interferes with both positive and negative selection. ADAP deficiency also impairs the ability of transgene-bearing DP thymocytes to form conjugates with Ag-loaded presenting cells. These findings suggest that ADAP is critical for thymocyte development and selection.

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Adaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsAntigen-Presenting CellsCD4 AntigensCD8 AntigensCalciumCell AdhesionCell DegranulationCell DifferentiationCell Line, TumorCell ProliferationFemaleLymphocyte CountMaleMiceMice, KnockoutMice, TransgenicMolecular Sequence DataT-Lymphocyte SubsetsThymus GlandJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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Jennifer N Wu, Shereen Gheith, Natalie A Bezman, Qing-Hua Liu, Lindsey V Fostel, Andrew M Swanson, Bruce D Freedman, Gary A Koretzky, Erik J Peterson. 2006-06-01. Adhesion- and degranulation-promoting adapter protein is required for efficient thymocyte development and selection.. https://doi.org/10.4049/jimmunol.176.11.6681

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