Trogocytic-molting of T-cell microvilli controls T-cell clonal expansion

Abstract

Abstract Internalization of the T-cell antigen receptor (TCR) is intimately linked to T-cell activation: a phenomenon thought to be related to the “exhaustion” of T-cell responses. To date, however, no report has considered that during physical interaction with cognate antigen-presenting cells, T cells release many TCRs via T-cell microvilli particles, which are derived from finger-like membrane structures (microvilli) in a combined process of trogocytosis and enzymatic vesiculation and correspond with the loss of membrane TCRs and many external membrane components. Surprisingly, in contrast to TCR internalization, this event leads to rapid upregulation of surface TCRs and remarkable metabolic reprogramming of cholesterol and fatty acids synthesis to meet the demands of clonal expansion, which drives multiple rounds of division and cell survival. We called this event “trogocytic-molting,” which represents an intrinsic molecular basis of T-cell clonal expansion by which T cells gain increased sensitivity to low antigen concentrations. This work was supported by the Creative Research Initiative Program (2015R1A3A2066253); Bio-Synergy Research Project (2021M3A9C4000991); Bio & Medical Technology Development Program [2020M3A9G3080281] through National Research Foundation (NRF) grants funded by the Ministry of Science and ICT (MSIT), the Basic Science Program (2019R1C1C1009570 & 2022R1A2C4002627) through National Research Foundation (NRF) grants funded by the Ministry of Education (MOE), and supported by Global University Project (GUP), GIST Research Institute (GRI) IBBR grant funded by the GIST (in 2021-2022), and the Joint Research Project of Institutes of Science and Technology (2021–2022), Korea.