TcR-alpha mRNA accumulation does not dictate cell surface TcR/CD3 expression.
The TcR-alpha chain is the last subunit of the TcR/CD3 complex to be expressed during thymic ontogeny. Since the presence of all subunits are required for efficient expression of this complex on the cell surface, this has lead to the hypothesis that the TcR-alpha chain is the limiting subunit which controls cell surface TcR/CD3 expression during thymocyte differentiation. We have examined this issue using a T-lymphoma cell clone, RS4.2, which has a CD4- CD8- Thyl+ J11d+ IL2R+ phenotype, identical with immature thymocytes which have the capacity to generate all major T cell subsets. The RS4.2 cell clone accumulates abundant amounts of TcR-beta, CD3-gamma, -delta, -epsilon and -zeta transcripts, but expresses trace levels of TcR-alpha transcripts and cell surface TcR/CD3. TcR-alpha mRNA levels can be dramatically augmented in RS4.2 cells by three distinct mechanisms: in response to treatment with either phorbol myristate acetate (PMA), calcium ionophore (A23187), or cycloheximide (CHX). However, the expression of TcR/CD3 on the cell surface fails to be increased by any of these agents. In fact, PMA induces a rapid down-regulation of cell surface TcR/CD3 expression. In contrast, these agents trigger an increase in cell surface IL2R expression which coincides with augmented IL2R-alpha mRNA levels. Thus, in RS4.2 cells, IL2R surface expression is controlled by transcript levels, while TcR/CD3 surface expression is regulated by post-transcriptional events, independent of TcR-alpha mRNA accumulation.
Herrick
T
T
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
Qian
L
L
Wilkinson
M F
MF
D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis*; D017252:CD3 Complex; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D012333:RNA, Messenger / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D000001:Calcimycin; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate