Unfolded protein response in the activation-induced biological processes of CD8⁺ T cells

As the central part of cellular immunity, primed CD8⁺ T cells go through different phases of response including activation, clonal expansion, contraction and steady-state turnover, which is accompanied by a fluctuating level of endoplasmic reticulum stress that leads to the elicitation of unfolded protein response (UPR). In turn, UPR casts profound impacts on the activation-induced biological processes of CD8⁺ T cells, which may greatly determine the magnitude and quality of T-cell based immunity. However, current understanding of the interconnectivity between UPR and T cell-biology is not comprehensive, with details of manipulation largely unexplored. In this review, the molecular basis of UPR involved in different stages of activated CD8⁺ T cells and its immunological significance are discussed, with potential strategies of regulation proposed, which may provide instructive guidance for the design and optimization of T cell-based immunotherapy.