{"doi":"10.1172/jci148979","title":"HLA-E–restricted HIV-1–specific CD8+ T cell responses in natural infection","abstract":"CD8+ T cell responses restricted by MHC-E, a nonclassical MHC molecule, have been associated with protection in an SIV/rhesus macaque model. The biological relevance of HLA-E-restricted CD8+ T cell responses in HIV infection, however, remains unknown. In this study, CD8+ T cells responding to HIV-1 Gag peptides presented by HLA-E were analyzed. Using in vitro assays, we observed HLA-E-restricted T cell responses to what we believe to be a newly identified subdominant Gag-KL9 as well as a well-described immunodominant Gag-KF11 epitope in T cell lines derived from chronically HIV-infected patients and also primed from healthy donors. Blocking of the HLA-E/KF11 binding by the B7 signal peptide resulted in decreased CD8+ T cell responses. KF11 presented via HLA-E in HIV-infected cells was recognized by antigen-specific CD8+ T cells. Importantly, bulk CD8+ T cells obtained from HIV-infected individuals recognized infected cells via HLA-E presentation. Ex vivo analyses at the epitope level showed a higher responder frequency of HLA-E-restricted responses to KF11 compared with KL9. Taken together, our findings of HLA-E-restricted HIV-specific immune responses offer intriguing and possibly paradigm-shifting insights into factors that contribute to the immunodominance of CD8+ T cell responses in HIV infection.","journal":"Journal of Clinical Investigation","year":2021,"id":169407,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"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":701209,"name":"Mika N. Gehre","orcid":null,"position":1,"is_corresponding":false},{"id":700286,"name":"Kai Qin","orcid":"0000-0003-1721-6054","position":2,"is_corresponding":false},{"id":491178,"name":"Sarah Sterrett","orcid":null,"position":3,"is_corresponding":false},{"id":700287,"name":"Ayub Ali","orcid":"0000-0002-3256-990X","position":4,"is_corresponding":false},{"id":547605,"name":"Ying Dang","orcid":null,"position":5,"is_corresponding":false},{"id":546875,"name":"Sojan Abraham","orcid":"0000-0002-7875-8220","position":6,"is_corresponding":false},{"id":347958,"name":"Margaret C. Costanzo","orcid":"0009-0008-5996-3924","position":7,"is_corresponding":false},{"id":700288,"name":"Leon A. Venegas","orcid":"0000-0002-7412-4618","position":8,"is_corresponding":false},{"id":385018,"name":"Jianming Tang","orcid":"0000-0003-0137-7486","position":9,"is_corresponding":false},{"id":701210,"name":"N. Manjunath","orcid":null,"position":10,"is_corresponding":false},{"id":440232,"name":"Mark A. Brockman","orcid":"0000-0001-6432-1426","position":11,"is_corresponding":false},{"id":377122,"name":"Otto O. Yang","orcid":"0000-0003-1970-8992","position":12,"is_corresponding":false},{"id":701211,"name":"June Kan‐Mitchell","orcid":null,"position":13,"is_corresponding":false},{"id":240555,"name":"Paul Goepfert","orcid":"0000-0001-8441-5737","position":14,"is_corresponding":false},{"id":385016,"name":"Anju Bansal","orcid":"0000-0002-8142-0386","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:46:15.560174Z","pmid":"34228645","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":[]}