{"doi":"10.1101/2021.10.19.464978","title":"T cell receptor and IL-2 signaling strength control memory CD8 <sup>+</sup> T cell functional fitness via chromatin remodeling","abstract":"Abstract Cognate antigen signal controls CD8 + T cell priming, expansion size and effector versus memory cell fates, but it is not known if and how it modulates the functional features of memory CD8 + T cells. Here we show that the strength of T cell receptor (TCR) signaling determines the requirement for interleukin-2 (IL-2) signals to form a pool of memory CD8 + T cells that competitively re-expand upon secondary antigen encounter. Combining strong TCR and intact IL-2 signaling synergistically induces genome-wide chromatin accessibility in regions targeting a wide breadth of biological processes, consistent with their greater functional fitness. Chromatin accessibility in promoters of genes encoding for stem cell, cell cycle and calcium-related proteins correlated with faster intracellular calcium accumulation, initiation of cell cycle and more robust expansion. High-dimensional flow-cytometry analysis also highlights higher subset diversity and phenotypes. These results formally establish that epitope selection in vaccine design strongly impacts memory CD8 + T cell epigenetic programming and functions. One Sentence Summary The strength of antigenic and interleukin 2 signals received by CD8 + T cells during vaccination epigenetically programs their ability to form functional memory.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":227154,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":745191,"name":"Erik Guillen","orcid":"0000-0001-7873-829X","position":1,"is_corresponding":false},{"id":745612,"name":"Laurent Chorro","orcid":null,"position":2,"is_corresponding":false},{"id":109649,"name":"Sooraj Achar","orcid":"0000-0003-3425-7501","position":3,"is_corresponding":false},{"id":831523,"name":"Karina Ng","orcid":null,"position":4,"is_corresponding":false},{"id":830952,"name":"Susanne Oberle","orcid":"0000-0002-0145-1829","position":5,"is_corresponding":false},{"id":272837,"name":"Francesca Alfei","orcid":null,"position":6,"is_corresponding":false},{"id":271014,"name":"Dietmar Zehn","orcid":"0000-0003-1393-8527","position":7,"is_corresponding":false},{"id":109653,"name":"Grégoire Altan‐Bonnet","orcid":"0000-0002-7283-3162","position":8,"is_corresponding":false},{"id":307677,"name":"Fabien Delahaye","orcid":"0000-0002-9921-8653","position":9,"is_corresponding":false},{"id":653328,"name":"Grégoire Lauvau","orcid":"0000-0002-3050-2664","position":10,"is_corresponding":false},{"id":745193,"name":"Shu Shien Chin","orcid":"0000-0002-2455-9533","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:54:42.179886Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}