{"doi":"10.17615/wg1x-r111","title":"Proteome-wide analysis of HIV-specific naive and memory CD4 + T cells in unexposed blood donors","abstract":"Healthy, uninfected individuals harbor HIV-specific naive and memory CD4+ T cells, and many memory T cell epitopes are similar in sequence to peptides expressed by natural commensal bacteria, suggesting potential cross-reactivity.The preexisting HIV-1–specific T cell repertoire must influence both the immunodominance of T cells after infection and immunogenicity of vaccines. We directly compared two methods for measuring the preexisting CD4+ T cell repertoire in healthy HIV-1–negative volunteers, the HLA-peptide tetramer enrichment and T cell library technique, and show high concordance (r = 0.989). Using the library technique, we examined whether naive, central memory, and/or effector memory CD4+ T cells specific for overlapping peptides spanning the entire HIV-1 proteome were detectable in 10 HLA diverse, HIV-1–unexposed, seronegative donors. HIV-1–specific cells were detected in all donors at a mean of 55 cells/million naive cells and 38.9 and 34.1 cells/million in central and effector memory subsets. Remarkably, peptide mapping showed most epitopes recognized by naive (88%) and memory (56%) CD4+ T cells had been previously reported in natural HIV-1 infection. Furthermore, 83% of epitopes identified in preexisting memory subsets shared epitope length matches (8–12 amino acids) with human microbiome proteins, suggestive of a possible cross-reactive mechanism. These results underline the power of a proteome-wide analysis of peptide recognition by human T cells for the identification of dominant antigens and provide a baseline for optimizing HIV-1–specific helper cell responses by vaccination.","journal":"UNC Libraries","year":2020,"id":135801,"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":0.9414,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":106118,"name":"Andrew J. McMichael","orcid":"0000-0002-9101-7478","position":1,"is_corresponding":false},{"id":249716,"name":"Nilu Goonetilleke","orcid":"0000-0003-2278-1656","position":2,"is_corresponding":false},{"id":24197,"name":"Bette Korber","orcid":"0000-0002-2026-5757","position":3,"is_corresponding":false},{"id":594005,"name":"Astrea Rossetti","orcid":null,"position":4,"is_corresponding":false},{"id":593338,"name":"Tess M. Brodie","orcid":"0000-0002-7934-138X","position":5,"is_corresponding":false},{"id":73799,"name":"Federica Sallusto","orcid":"0000-0003-3750-2752","position":6,"is_corresponding":false},{"id":109932,"name":"William A. Fischer","orcid":"0000-0002-4900-098X","position":7,"is_corresponding":false},{"id":272609,"name":"Suzanne Campion","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:35.237665Z","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":[]}