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Adhesion- and Degranulation-Promoting Adapter Protein Is Required for Efficient Thymocyte Development and Selection¹

Jennifer N. Wu^*, Shereen Gheith^*, Natalie A. Bezman^*, Qing-Hua Liu, Lindsey V. Fostel, Andrew M. Swanson, Bruce D. Freedman, Gary A. Koretzky^2,* and Erik J. Peterson

^* Abramson Family Cancer Research Institute and Department of Laboratory Medicine and Pathology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; and Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, MN 55455

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, _L2). 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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