Related Experiment Video
Updated: Apr 27, 2026
Co-Culture and Transduction of Murine Thymocytes on Delta-Like 4-Expressing Stromal Cells to Study Oncogenes in T-Cell Leukemia
Published on: June 9, 2023
Mammalian target of rapamycin complex 2 modulates αβTCR processing and surface expression during thymocyte
Po-Chien Chou1, Won Jun Oh1, Chang-Chih Wu1
1Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854;
Abstract:
An efficient immune response relies on the presence of T cells expressing a functional TCR. Whereas the mechanisms generating TCR diversity for antigenic recognition are well defined, what controls its surface expression is less known. In this study, we found that deletion of the mammalian target of rapamycin complex (mTORC) 2 component rictor at early stages of T cell development led to aberrant maturation and increased proteasomal degradation of nascent TCRs. Although CD127 expression became elevated, the levels of TCRs as well as CD4, CD8, CD69, Notch, and CD147 were significantly attenuated on the surface of rictor-deficient thymocytes. Diminished expression of these receptors led to suboptimal signaling, partial CD4(-)CD8(-) double-negative 4 (CD25(-)CD44(-)) proliferation, and CD4(+)CD8(+) double-positive activation as well as developmental blocks at the CD4(-)CD8(-) double-negative 3 (CD25(+)CD44(-)) and CD8-immature CD8(+) single-positive stages. Because CD147 glycosylation was also defective in SIN1-deficient fibroblasts, our findings suggest that mTORC2 is involved in the co/posttranslational processing of membrane receptors. Thus, mTORC2 impacts development via regulation of the quantity and quality of receptors important for cell differentiation.
Insights
Deletion of mTORC2 component rictor impairs T cell development by reducing surface receptor expression. This leads to aberrant maturation and developmental blocks in thymocytes, impacting immune response.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- T cell receptor (TCR) diversity is crucial for immune response.
- Mechanisms controlling TCR surface expression are less understood than TCR diversity generation.
Purpose of the Study:
- To investigate the role of mTORC2 in T cell development and receptor surface expression.
- To understand how rictor deletion affects T cell maturation and signaling.
Main Methods:
- Studied T cell development in mice lacking the rictor component of mTORC2.
- Analyzed surface expression of TCR and other key receptors (CD4, CD8, CD69, Notch, CD147) on thymocytes.
- Assessed T cell proliferation and developmental progression.
Main Results:
- Rictor deletion caused aberrant T cell maturation and increased TCR proteasomal degradation.
- Surface levels of TCR, CD4, CD8, CD69, Notch, and CD147 were significantly reduced.
- Defective receptor expression led to impaired signaling, proliferation, and developmental blocks at multiple thymocyte stages.
Conclusions:
- mTORC2, via rictor, is essential for proper T cell development.
- mTORC2 regulates the co/posttranslational processing and surface expression of membrane receptors.
- Rictor-mediated mTORC2 signaling impacts T cell differentiation by controlling receptor quantity and quality.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:16TGF - β Signaling Pathway
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
01:26Receptor Tyrosine Kinases