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Published on: January 15, 2011
CD81 expressed on human thymocytes mediates integrin activation and interleukin 2-dependent proliferation
1Department of Biology and Molecular Biology Institute, San Diego State University, California 92182-4614, USA.
Insights
CD81, or target of antiproliferative antigen (TAPA)-1, associates with T cell coreceptors in human thymocytes. This interaction promotes cell adhesion and costimulates T cell activation, suggesting a regulatory role in thymocyte development.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- T cell receptor (TCR) and coreceptor signaling regulate lymphocyte adhesion and function.
- CD81 (target of antiproliferative antigen [TAPA]-1) is a cell surface protein with known roles in cell proliferation and adhesion.
Purpose of the Study:
- To investigate the expression and function of CD81 in human thymocytes.
- To determine the association of CD81 with T cell coreceptors (CD4 and CD8).
- To elucidate the role of CD81 in regulating thymocyte adhesion and activation.
Main Methods:
- Immunohistochemistry to detect CD81 expression on human thymocytes.
- Co-immunoprecipitation to assess the physical association of CD81 with CD4 and CD8 coreceptors.
- Flow cytometry to measure integrin-mediated cell-cell adhesion (LFA-1) and T cell proliferation following CD81 ligation.
Main Results:
- CD81 is expressed on human thymocytes and physically associates with CD4 and CD8 coreceptors.
- Antibody-mediated ligation of CD81 rapidly induces integrin-mediated cell-cell adhesion via LFA-1.
- Cross-linking CD81 acts as a costimulatory signal with TCR/CD3, leading to interleukin-2-dependent thymocyte proliferation.
Conclusions:
- CD81 plays a significant role in regulating human thymocyte adhesion and activation.
- A CD81-mediated signaling pathway contributes to the control of cell adhesion and immune cell activation during thymocyte development.
Abstract:
Lymphocyte recognition of antigen by the antigen-specific T cell receptor (TCR) and coreceptor complexes rapidly alters the cell's adhesive properties facilitating high avidity cell-ligand interactions necessary for lymphocyte development and function. Here, we report the expression of CD81 (target of antiproliferative antigen [TAPA]-1) on human thymocytes and the physical association of CD81 with CD4 and CD8 T cell coreceptors. Antibody ligation of CD81 on thymocytes promotes the rapid induction of integrin-mediated cell-cell adhesion via lymphocyte function-associated molecule-1 (LFA-1). Cross-linking CD81 is also shown to be costimulatory with signaling through the TCR/CD3 complex inducing interleukin 2-dependent thymocyte proliferation. These data suggest that a CD81-mediated pathway in thymocytes is involved in the regulation of both cell adhesion and activation.
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