An efficient immune response relies on the presence of T-cells expressing a functional T-cell receptor (TCR). While the mechanisms generating TCR diversity for antigenic recognition are well defined, what controls its surface expression is less known. Here we found that mTOR complex 2 (mTORC2) modulates T-cell ontogeny by controlling the quantity of TCR that reaches the cell surface. Deletion of the mTORC2 component rictor at early stages of T-cell development led to aberrant maturation and increased proteasomal degradation of nascent TCR polypeptides. Consequently, the levels of TCR as well as other receptors, including CD4, CD8 and CD147 were significantly attenuated on the surface of rictor-deficient thymocytes. Since CD147 was also defectively glycosylated and expressed in SIN1-deficient fibroblasts, our findings suggest that mTORC2 is involved in the co/post-translational processing of membrane receptors. Thus, this novel function for mTORC2 provides a rationale to target this complex in disorders caused by deregulated expression of surface receptors.
- Copyright © 2013 by The American Association of Immunologists, Inc.