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Adhesion- and degranulation-promoting adapter protein is required for efficient thymocyte development and selection.
Jennifer N Wu1, Shereen Gheith, Natalie A Bezman
1Abramson Family Cancer Research Institute and Department of Laboratory Medicine and Pathology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|May 20, 2006
Summary
Adhesion- and degranulation-promoting adapter protein (ADAP) is crucial for T cell activation and development. Its absence impairs T cell proliferation, selection, and conjugate formation, highlighting ADAP
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Adhesion- and degranulation-promoting adapter protein (ADAP) plays a known role in T cell receptor (TCR)-induced activation and proliferation.
- ADAP is also involved in the TCR-initiated, inside-out activation of the integrin LFA-1.
Purpose of the Study:
- To investigate the role of ADAP in thymocyte development and selection.
- To determine the impact of ADAP deficiency on T cell activation and proliferation within the thymus.
Main Methods:
- Analysis of ADAP-deficient CD4/CD8 double-positive (DP) thymocytes.
- Assessment of CD69 upregulation in DP thymocytes in vivo.
- Utilized MHC class I- and class II-restricted TCR transgenic models.
- Examined conjugate formation between DP thymocytes and antigen-presenting cells.
Main Results:
- ADAP-deficient DP cells exhibited diminished proliferation and poor CD69 upregulation.
- Loss of ADAP impaired both positive and negative selection in TCR transgenic models.
- ADAP deficiency reduced the ability of DP thymocytes to form conjugates with antigen-presenting cells.
Conclusions:
- ADAP is essential for normal thymocyte development and selection processes.
- ADAP plays a critical role in T cell activation, proliferation, and thymic selection.