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

Po Chien Chou, Won Jun Oh, Chang Chih Wu, Joseph Moloughney, Markus A. Ruegg, Michael N. Hall, Estela Jacinto, Guy Werlen

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 CD42CD82 doublenegative 4 (CD252CD442) proliferation, and CD4+CD8+ double-positive activation as well as developmental blocks at the CD42CD82 double-negative 3 (CD25+CD442) 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.

Original languageEnglish (US)
Pages (from-to)1162-1170
Number of pages9
JournalJournal of Immunology
Volume193
Issue number3
DOIs
StatePublished - Aug 1 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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