Folding for the Immune Synapse: CCT Chaperonin and the Cytoskeleton.

Lymphocytes rearrange their shape, membrane receptors and organelles during cognate contacts with antigen-presenting cells (APCs). Activation of T cells by APCs through pMHC-TCR/CD3 interaction (peptide-major histocompatibility complex-T cell receptor/CD3 complexes) involves different steps that lead to the reorganization of the cytoskeleton and organelles and, eventually, activation of nuclear factors allowing transcription and ultimately, replication and cell division. Both the positioning of the lymphocyte centrosome in close proximity to the APC and the nucleation of a dense microtubule network beneath the plasma membrane from the centrosome support the T cell's intracellular polarity. Signaling from the TCR is facilitated by this traffic, which constitutes an important pathway for regulation of T cell activation. The coordinated enrichment upon T cell stimulation of the chaperonin CCT (chaperonin-containing tailless complex polypeptide 1; also termed TRiC) and tubulins at the centrosome area support polarized tubulin polymerization and T cell activation. The proteasome is also enriched in the centrosome of activated T cells, providing a mechanism to balance local protein synthesis and degradation. CCT assists the folding of proteins coming from de novo synthesis, therefore favoring mRNA translation. The functional role of this chaperonin in regulating cytoskeletal composition and dynamics at the immune synapse is discussed. ; This work was supported bun the ALBA Synchrotron standard proposals 2015021148 and 2016021638 to NM-C and JMV. This study was supported by grants SAF2017-82886-R (to FS-M) and PID2019-105872GB-I00/AEI/10.13039/501100011033 (AEI/FEDER, UE) (to JMV) from the Spanish Ministry of Economy and Competitiveness (MINECO), grants INFLAMUNE-S2017/BMD-23671 (to FS-M) and P2018/NMT-4389 (to JMV) from the Comunidad de Madrid, ERC-2011-AdG 294340-GENTRIS (to FS-M), a 2019 grant from the Ramón Areces Foundation “Ciencias de la Vida y la Salud” and a 2018 grant from Ayudas Fundación BBVA a Equipos de ...