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

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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, αLβ2). In this study, we demonstrate that ADAP-deficient CD4/CD8 doubl-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.

Original languageEnglish (US)
Pages (from-to)6681-6689
Number of pages9
JournalJournal of Immunology
Volume176
Issue number11
DOIs
StatePublished - Jun 1 2006

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