{"doi":"10.1101/2021.04.28.441880","title":"Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence","abstract":"ABSTRACT CD8+ T cells are important antiviral effectors that can potentiate long-lived immunity against COVID-19, but a detailed characterization of these cells has been hampered by technical challenges. We screened 21 well-characterized, longitudinally-sampled convalescent donors that recovered from mild COVID-19 against a collection of SARS-CoV-2 tetramers, and identified one participant with an immunodominant response against Nuc 322-331 , a peptide that is conserved in all the SARS-CoV-2 variants-of-concern reported to date. We conducted 38- parameter CyTOF phenotyping on tetramer-identified Nuc 322-331 -specific CD8+ T cells, and on CD4+ and CD8+ T cells recognizing the entire nucleocapsid and spike proteins from SARS- CoV-2, and took 32 serological measurements on longitudinal specimens from this participant. We discovered a coordination of the Nuc 322-331 -specific CD8+ T response with both the CD4+ T cell and antibody pillars of adaptive immunity. Nuc 322-331 -specific CD8+ T cells were predominantly central memory T cells, but continually evolved over a ∼6-month period of convalescence. We observed a slow and progressive decrease in the activation state and polyfunctionality of the Nuc 322-331 -specific CD8+ T cells, accompanied by an increase in their lymph-node homing and homeostatic proliferation potential. These results suggest that following a typical case of mild COVID-19, SARS-CoV-2-specific CD8+ T cells not only persist but continuously differentiate in a coordinated fashion well into convalescence, into a state characteristic of long-lived, self-renewing memory.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215406,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"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":722047,"name":"Heeju Ryu","orcid":"0000-0002-4742-5415","position":1,"is_corresponding":false},{"id":246062,"name":"Matthew McGregor","orcid":"0000-0002-1547-5063","position":2,"is_corresponding":false},{"id":418251,"name":"Benjamin Babcock","orcid":"0000-0002-2902-8045","position":3,"is_corresponding":false},{"id":246058,"name":"Jason Neidleman","orcid":"0000-0003-3525-8047","position":4,"is_corresponding":false},{"id":246059,"name":"Guorui Xie","orcid":"0000-0002-9295-2724","position":5,"is_corresponding":false},{"id":246063,"name":"Ashley F. George","orcid":"0000-0002-1482-5244","position":6,"is_corresponding":false},{"id":71685,"name":"Julie Frouard","orcid":"0000-0002-6296-2534","position":7,"is_corresponding":false},{"id":636294,"name":"Victoria Murray","orcid":"0000-0002-4479-2359","position":8,"is_corresponding":false},{"id":246060,"name":"Gurjot Gill","orcid":"0000-0002-3207-6582","position":9,"is_corresponding":false},{"id":108301,"name":"Eliver Ghosn","orcid":"0000-0001-7258-906X","position":10,"is_corresponding":false},{"id":272540,"name":"Evan W. Newell","orcid":"0000-0002-2889-243X","position":11,"is_corresponding":false},{"id":75994,"name":"Sulggi A. Lee","orcid":"0000-0003-1560-2250","position":12,"is_corresponding":false},{"id":71692,"name":"Nadia R. Roan","orcid":"0000-0002-5464-1976","position":13,"is_corresponding":false},{"id":248465,"name":"Tongcui Ma","orcid":null,"position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:55.971300Z","pmid":"33948597","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":[]}