The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function
Oftedal, Bergithe Eikeland; Maio, Stefano; Handel E, Adam; White PJ, Madeleine; Howie, Duncan; Davis, Simon; Prevot, Nicolas; Rota A, Ioanna; Deadman E, Mary; Kessler M, Benedict; Fischer, Roman; Trede S, Nikolaus; Sezgin, Erdinc; Maizels M, Rick; Holländer, Georg A.
Journal article, Peer reviewed
Published version
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Date
2021Metadata
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- Department of Clinical Science [2293]
- Registrations from Cristin [9487]
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.