Chaperonin CCT8 is essential for T cell development and function

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. Here we demonstrate that the eukaryotic type II chaperonin complex CCT is indispensable for T cell development, function, stress-response, and metabolism. CCT-deficient thymoyctes are compromised in their selection, differentiation, and late stage maturation. The lack of CCT expression prevents a normal response to T cell activation induced changes in the proteome, stops the formation of nuclear actin filaments and impairs a normal cells stress response. Consequently, T cell homeostatic maintenance and receptor-mediated stimulation of proliferation are impaired in CCT-deficient T cells leading to activation-induced cell death. Furthermore, Th2 polarization digresses in the absence of CCT-controlled protein folding leading paradoxically to continued IFN-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. Taken together, these findings demonstrate that both normal thymopoiesis and peripheral T cell biology are critically dependent on CCT-controlled proteostasis and that its absence is incompatible with protective immunity.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): T-lymphocyte

SUBMITTER: Simon Davis  

LAB HEAD: Roman Fischer

PROVIDER: PXD018834 | Pride | 2021-09-09

REPOSITORIES: Pride