Fig. 1: PSR is triggered in Tex cells with a dynamic expression of chaperone proteins. | Nature

Fig. 1: PSR is triggered in Tex cells with a dynamic expression of chaperone proteins.

From: Proteotoxic stress response drives T cell exhaustion and immune evasion

Fig. 1

a, Schematic of the experiment to isolate mouse splenic LCMV antigen-specific CD8+ T cell subpopulations in LCMV acute (Armstrong (Arm)) and chronic (clone 13 (Cl13)) infection models. b, Heatmap of expression levels of proteins belonging to 11 T cell signatures across 9 groups (n = 3–4, representing pooled 5–15 mice per replicate). D, day. c, Heatmap of the expression profiles of 5,284 proteins quantified in naive T cells, acutely activated T cells (Teff) and chronically activated T cells (Tex) at 2, 4, 6 and 8 days after initial activation, as described in Extended Data Fig. 1a, with k-means clustering identifying 8 distinct expression patterns (n = 4, each replicate was pooled from 3 mice). d, Enrichment analysis of proteins from cluster 6 defined in c (one-sided Fisher’s exact test with Benjamini–Hochberg correction). e, Heatmap of expression levels of proteins belonging to 12 gene ontology terms. f, Schematic of MS-based proteomic analysis of CD8+ T cells in different exhaustion states from the MC38 colon cancer mouse model and the MB49 bladder tumour mouse model. s.c., subcutaneous. g, Principal component analysis plots of proteomes of Tprog, Tint and Ttex cells (n = 3, each biological replicate was pooled from 12–13 mice). h, Heatmap of protein expression across eight gene ontologies in three CD8+ T cell subpopulations from MC38 and MB49 tumour models. i, Bubble plot of the expression levels of protein-folding chaperones in naive, Teff and Tex CD8+ T cells generated in vitro as described in Extended Data Fig. 1a. The bubble colour intensity is proportional to the protein expression level. The bubble size is proportional to the absolute z score value. j, Heatmap of the expression levels of chaperone proteins (defined in i) in three CD8+ T cell subpopulations from MC38 and MB49 tumours. The diagrams in a and f were created using BioRender (https://www.biorender.com).

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