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TcR-alpha mRNA accumulation does not dictate cell surface TcR/CD3 expression
T Herrick1, L Qian, M F Wilkinson
1Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
Molecular Immunology
|April 1, 1992
Summary
T-cell receptor alpha chain (TcR-alpha) is not the limiting factor for TcR/CD3 complex expression on thymocytes. Post-transcriptional regulation, not TcR-alpha mRNA levels, controls cell surface TcR/CD3 expression.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- The T-cell receptor (TcR)/CD3 complex is crucial for T-cell development and function.
- TcR-alpha chain expression is the final step in TcR/CD3 complex assembly during thymic ontogeny.
- It was hypothesized that TcR-alpha is the limiting subunit for cell surface TcR/CD3 expression.
Purpose of the Study:
- To investigate the role of the TcR-alpha chain in controlling cell surface TcR/CD3 expression.
- To determine the regulatory mechanisms of TcR/CD3 surface expression in immature T cells.
Main Methods:
- Utilized the T-lymphoma cell clone RS4.2, mimicking immature thymocytes.
- Analyzed TcR-alpha mRNA and cell surface TcR/CD3 expression.
- Examined the effects of phorbol myristate acetate (PMA), calcium ionophore (A23187), and cycloheximide (CHX) on gene and protein expression.
Main Results:
- RS4.2 cells accumulated TcR-beta and CD3 transcripts but had low TcR-alpha mRNA and cell surface TcR/CD3.
- PMA, A23187, and CHX increased TcR-alpha mRNA but not cell surface TcR/CD3.
- PMA down-regulated cell surface TcR/CD3, while IL2R expression increased with its mRNA levels.
Conclusions:
- TcR/CD3 surface expression in RS4.2 cells is regulated by post-transcriptional events, independent of TcR-alpha mRNA levels.
- Interleukin-2 receptor (IL2R) surface expression is controlled by transcript levels, unlike TcR/CD3.
- This suggests distinct regulatory pathways for TcR/CD3 and IL2R surface expression during T-cell differentiation.