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

• Published in: Journal of Immunology Vol. 176; no. 11; pp. 6681 - 6689
• Main Authors: Wu, Jennifer N, Gheith, Shereen, Bezman, Natalie A, Liu, Qing-Hua, Fostel, Lindsey V, Swanson, Andrew M, Freedman, Bruce D, Koretzky, Gary A, Peterson, Erik J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.06.2006
• Subjects: Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Amino Acid Sequence; Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Calcium - metabolism; CD4 Antigens - biosynthesis; CD8 Antigens - biosynthesis; Cell Adhesion - genetics; Cell Adhesion - immunology; Cell Degranulation - genetics; Cell Degranulation - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Line, Tumor; Cell Proliferation; Female; Lymphocyte Count; Male; Mice; Mice, Knockout; Mice, Transgenic; Molecular Sequence Data; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - metabolism
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.176.11.6681

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.