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The Role of mTORC2 in T-Cell Development

by
Po-Chien Chou
M.S., National Chung-Hsing University 2003

Thesis Advisor: Estela Jacinto, Ph.D
Graduate Program in Physiology and Integrated Biology

Conference Room 258
School of Public Health
Piscataway

Thursday, April 14, 2011
9:30 a.m.


Abstract

An efficient immune response relies on the presence of T-lymphocytes expressing a functional T-cell receptor (TCR). While the mechanisms generating TCR diversity for antigenic recognition are well defined, what controls TCR expression at the cell surface is less known. Here we found that mTOR complex 2 (mTORC2) modulates T-cell ontogeny by controlling the quantity of TCRs that reach the surface of maturing T-cells. By deleting the mTORC2 component rictor at early stages of T-cell development, we found increased proteasomal degradation of nascent TCR polypeptides that causes a significant reduction in receptor at the cell surface. This was accompanied by enhanced unfolded protein response, suggesting that mTORC2 is involved in the processing of membrane receptors. Reduced TCR surface expression severely affected thymocyte homeostasis and impeded T-cell differentiation. Thus, we uncover a novel function for mTORC2 that provides rationale to target this complex in defining new treatment for T-cell lymphoma and other T-cell related disorders in which surface receptor expression is deregulated.


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