The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function

Commun Biol. 2021 Jun 3;4(1):681. doi: 10.1038/s42003-021-02203-0.

Abstract

T cells rely for their development and function on the correct folding and turnover of proteins generated in response to a broad range of molecular cues. In the absence of the eukaryotic type II chaperonin complex, CCT, T cell activation induced changes in the proteome are compromised including the formation of nuclear actin filaments and the formation of a normal cell stress response. Consequently, thymocyte maturation and selection, and T cell homeostatic maintenance and receptor-mediated activation are severely impaired. In the absence of CCT-controlled protein folding, Th2 polarization diverges from normal differentiation with paradoxical continued IFN-γ expression. As a result, CCT-deficient T cells fail to generate an efficient immune protection against helminths as they are unable to sustain a coordinated recruitment of the innate and adaptive immune systems. These findings thus demonstrate that normal T cell biology is critically dependent on CCT-controlled proteostasis and that its absence is incompatible with protective immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Chaperonin Containing TCP-1 / genetics
  • Chaperonin Containing TCP-1 / immunology*
  • Chaperonin Containing TCP-1 / metabolism
  • Humans
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proteome / immunology
  • Proteome / metabolism
  • Proteostasis / genetics
  • Proteostasis / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymocytes / cytology
  • Thymocytes / immunology*
  • Thymocytes / metabolism
  • Transcriptome / genetics
  • Transcriptome / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Proteome
  • Tumor Necrosis Factor-alpha
  • Chaperonin Containing TCP-1