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Published on: December 11, 2007
The receptor function of CD2 in human CD2 transgenic mice is based on highly conserved associations with signal
M K Wild1, A M Verhagen, S C Meuer
1Institute for Immunology, Ruprecht-Karls-Universität, Heidelberg, Germany.
Insights
This study shows that human CD2 (huCD2) engages similar signaling proteins in both human and transgenic mouse T cells. This suggests conserved molecular mechanisms for T cell activation via CD2 in different species.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- T cell activation via CD2 typically requires specific monoclonal antibodies (mAbs) targeting distinct epitopes.
- Understanding the molecular interactions of CD2 is crucial for T cell activation research.
Purpose of the Study:
- To investigate the proliferative response of human and transgenic mouse T cells to novel CD2 mAbs.
- To map the epitopes of mitogenic CD2 mAbs using CD2:CD58 chimeric proteins.
- To analyze the molecular interactions of human CD2 (huCD2) with signaling proteins in transgenic murine T cells.
Main Methods:
- Examined T cell proliferation using novel CD2 monoclonal antibodies (AICD2.M1 and AICD2.M2).
- Epitope mapping of CD2 mAbs utilizing CD2:CD58 chimeric proteins.
- Analyzed molecular associations between huCD2 and signaling proteins in transgenic murine T cells via co-immunoprecipitation.
Main Results:
- Identified novel mitogenic CD2 mAbs and partially mapped their epitopes.
- Demonstrated that transgenic huCD2 interacts with murine tyrosine kinases (p56lck, p59fyn) and TCR/CD3 signaling complex components (CD3-epsilon, zeta chains).
- Observed co-immunoprecipitation of tyrosine phosphatase activity with huCD2, similar to human T cells.
Conclusions:
- Human CD2 couples to conserved signal transduction pathways in both human and transgenic mouse T cells.
- The molecular interactions of huCD2 in transgenic mice mirror those in human T cells, validating the model system.
- These findings provide insights into the molecular basis of T cell activation mediated by CD2.
Abstract:
The activation of human T cells via CD2 in response to mitogenic monoclonal antibodies (mAbs) typically requires that one mAb is specific for an epitope within the N-terminal Ig domain of CD2 and the other for a partially hidden epitope. We have examined the proliferative response of human T cells and human CD2 (huCD2) transgenic murine T cells to two novel CD2 monoclonal antibodies, AICD2.M1 and AICD2.M2, and have partially mapped the epitopes of these and other mitogenic CD2-specific monoclonal antibodies by way of recognition of CD2:CD58 chimeric proteins possessing either the N-terminal or the membrane proximal immunoglobulin domains of CD2. To understand the molecular basis of proliferation in huCD2 transgenic murine T cells, the interactions of huCD2 with signaling proteins in murine T cells were analyzed. The transgenic huCD2 molecule was found to interact with the murine tyrosine kinases p56lck and p59fyn and the CD3-epsilon and zeta chains of the TCR/CD3 signaling complex and to coimmunoprecipitate tyrosine phosphatase activity. These molecular associations resemble the situation in human T cells and suggest that human CD2 couples to the same signal transduction pathways in humans and transgenic mice.
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