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

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-gamma 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. Oftedal et al. generate mice lacking the chaperonin subunit CCT8 in T cells. They find that loss of CCT8 leads to reduced formation of nuclear actin filaments, changes in proteostasis, defective Th2 cell polarization and T cell metabolism and a failed antigenic response to intestinal helminths.

Automated summary

This study shows that the absence of the chaperonin subunit CCT8 in T cells severely impairs T cell activation, differentiation, and immune function. The deficiency in CCT-controlled protein folding leads to abnormal cellular stress response and inefficient immune protection against pathogens such as helminths.