Membrane shedding promotes the mTOR pathway in T Cells and enhances clonal expansion 3488

Abstract Description When T cells establish an immunological synapse with antigen-presenting cells (APCs), they release surface membrane fragments enriched with TCR micro-clusters. This membrane shedding, induced by T cell-target cell contact, delivers materials and information from T cells to other cells in particle form. Recent studies have revealed that T cells enhance their clonal expansion via this membrane shedding. However, the mechanism by which membrane release upregulates T cell proliferation remains unclear. Using various adhesion matrices and chemical compounds, we mimicked membrane shedding and observed that release of microvilli from the T cell surface during activation affects the mTOR pathway. Membrane shedding through surface microvilli altered the lipid composition of T cells, promoted phosphorylation of phosphoinositide 3-kinase (PI3K), and upregulated mTOR-related signaling pathways, driving T cell clonal expansion. Conversely, suppression of T cell microvilli shedding led to weakened mTOR signaling and impaired clonal expansion. Our findings demonstrate that contact between T cells and APCs induces T cell surface membrane release, which provides essential signals for clonal expansion. Furthermore, we propose that membrane shedding is not a disadvantageous loss of cellular components but rather an active mechanism intrinsic to T cell proliferation. Funding Sources Supported by National Research Foundation of Korea (NRF) grant; N40020; N38190 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)