Adhesion and Degranulation-Promoting Adapter Protein (ADAP) Positively Regulates T Cell Sensitivity to Antigen and T Cell Survival

• Published in: Journal of Immunology Vol. 179; no. 6; pp. 3559 - 3569
• Main Authors: Mueller, Kristen L, Thomas, Molly S, Burbach, Brandon J, Peterson, Erik J, Shimizu, Yoji
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.09.2007
• Subjects: Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Animals; Antigen Presentation - immunology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens, CD - biosynthesis; Antigens, Differentiation, T-Lymphocyte - biosynthesis; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Adhesion - immunology; Cell Degranulation - immunology; Cell Proliferation; Cell Survival - immunology; Cells, Cultured; Clone Cells; Dose-Response Relationship, Immunologic; Epitopes, T-Lymphocyte - immunology; Integrins - physiology; Interleukin-2 - biosynthesis; Interleukin-2 Receptor alpha Subunit - biosynthesis; Lectins, C-Type; Lymphocyte Activation - immunology; Lymphocyte Function-Associated Antigen-1 - physiology; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.179.6.3559

The hemopoietic specific adapter protein ADAP (adhesion and degranulation-promoting adapter protein) positively regulates TCR-dependent, integrin-mediated adhesion and participates in signaling pathways downstream of the TCR that result in T cell activation. The specific role of ADAP in regulating Ag-dependent T cell interactions with APCs and T cell activation following Ag stimulation is not known. We used ADAP-/- DO11.10 T cells to demonstrate that ADAP promotes T cell conjugation to Ag-laden APCs. Complementary in vitro and in vivo approaches reveal that ADAP controls optimal T cell proliferation, cytokine production, and expression of the prosurvival protein Bcl-xL in response to limiting Ag doses. Furthermore, ADAP is critical for clonal expansion in vivo independent of Ag concentration under conditions of low clonal abundance. These results suggest that ADAP regulates T cell activation by promoting Ag-dependent T cell-APC interactions, resulting in enhanced T cell sensitivity to Ag, and by participating in prosurvival signaling pathways initiated by Ag stimulation.