{"doi":"10.1126/sciadv.aea8707","title":"Unconventional CD8 <sup>+</sup> T cell surveillance of cytomegalovirus via Qa-1/HLA-E–restricted epitope recognition","abstract":"Nonclassical CD8 + T cells can compensate for classical CD8 + T cell effector responses during murine cytomegalovirus (MCMV) infection. Through a combination of motif-based discovery, predictive algorithms, AlphaFold3 structural modeling, and biological assays, we identified multiple MCMV and human cytomegalovirus (HCMV) peptides that bind to Qa-1 and HLA-E, respectively. In the mouse system, we demonstrated that these virally encoded antigens stimulate Qa-1–restricted CD8 + T cells ex vivo, which can be tracked using MCMV peptide–loaded Qa-1 tetramers. Adoptive transfer of predominantly Qa-1 tetramer + CD8 + T cells into RAG-1–deficient mice protects them from mortality, underscoring the critical role of these cells in host defense. Single-cell RNA (scRNA)/TotalSeq and single-cell T cell receptor sequencing (scTCR-seq) reveal the expansion of unique TCR αβ clonotypes, indicating convergent antigen specificity. Together, our findings uncover a conserved and functionally important nonclassical CD8 + T cell axis mediated by Qa-1/HLA-E modulating adaptive immunity independent of classical major histocompatibility complex class I (MHC-I) pathways and present previously unidentified opportunities for vaccine development.","journal":"Science Advances","year":2025,"id":535827,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1300948,"name":"Madison L. Smith","orcid":"0009-0000-4651-4777","position":1,"is_corresponding":false},{"id":793862,"name":"Samantha Borys","orcid":"0000-0003-4960-131X","position":2,"is_corresponding":false},{"id":684172,"name":"Céline Fugère","orcid":null,"position":3,"is_corresponding":false},{"id":1420525,"name":"Delia Demers","orcid":null,"position":4,"is_corresponding":false},{"id":230176,"name":"Michael J. Hogan","orcid":"0000-0002-6244-2993","position":5,"is_corresponding":false},{"id":21637,"name":"David Zemmour","orcid":"0000-0002-0990-217X","position":6,"is_corresponding":false},{"id":316857,"name":"Laurent Brossay","orcid":"0000-0002-7497-8488","position":7,"is_corresponding":false},{"id":1046268,"name":"Shanelle P. Reilly","orcid":"0000-0001-9465-706X","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T02:52:00.885532Z","pmid":"41417899","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":[]}