Mammalian target of rapamycin complex 2 modulates αβTCR processing and surface expression during thymocyte development

Chou, Po-Chien and Oh, Won Jun and Wu, Chang-Chih and Moloughney, Joseph and Rüegg, Markus A. and Hall, Michael N. and Jacinto, Estela and Werlen, Guy. (2014) Mammalian target of rapamycin complex 2 modulates αβTCR processing and surface expression during thymocyte development. Journal of Immunology, 193 (3). pp. 1162-1170.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Hall, Michael N. and Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association of Immunologists
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:12 Apr 2019 14:18
Deposited On:10 Oct 2014 09:19

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