{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294111"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A post-translational regulatory map of chronic antigen-driven human T cell dysfunction","description":"T cells exposed to persistent antigen, either in the context of chronic viral infections or tumors, iteratively lose both self-renewal and cytotoxic capacity. Several transcriptional, epigenetic, and metabolic drivers of this process have been identified. However, the post-transcriptional regulatory mechanisms influencing the proteome of dysfunctional T cells are not well understood. Here we present a time-resolved cysteine reactivity landscape of human T cells during the development of chronic antigen-driven dysfunction. Persistent T cell receptor stimulation of human T cells following activation significantly remodeled the T cell proteome compared with cytokine-mediated expansion, including changes in canonical T cell exhaustion-associated proteins as well as proteins related to mitochondrial function, redox homeostasis, nucleotide metabolism, and cell cycle progression. Exhausted T cells displayed frequent reactivity changes in nucleotide-binding domains across several protein classes that were associated with progressive loss of mitochondrial ATP production and activation of nucleotide salvage. Our comprehensive proteomic resource thus reveals a unique set of post-transcriptional changes as part of an exhausted T cell program and lays the groundwork for novel cysteine-directed therapeutics to enhance cancer immunotherapy.","dates":{"publication":"2026/04/15"},"accession":"GSE294111","cross_references":{"GSM":["GSM8898842","GSM8898843","GSM8898840","GSM8898841","GSM8898846","GSM8898835","GSM8898836","GSM8898847","GSM8898844","GSM8898845","GSM8898834","GSM8898839","GSM8898848","GSM8898837","GSM8898838"],"GPL":["24676"],"GSE":["294111"],"taxon":["Homo sapiens"]}}