{"doi":"10.1038/s42003-024-07350-8","title":"The identification of a SARs-CoV2 S2 protein derived peptide with super-antigen-like stimulatory properties on T-cells","abstract":"Severe COVID-19 can trigger a cytokine storm, leading to acute respiratory distress syndrome (ARDS) with similarities to superantigen-induced toxic shock syndrome. An outstanding question is whether SARS-CoV-2 protein sequences can directly induce inflammatory responses. In this study, we identify a region in the SARS-CoV-2 S2 spike protein with sequence homology to bacterial super-antigens (termed P3). Computational modeling predicts P3 binding to sites on MHC class I/II and the TCR that partially overlap with sites for the binding of staphylococcal enterotoxins B and H. Like SEB and SEH derived peptides, P3 stimulated 25-40% of human CD4+ and CD8 + T-cells, increasing IFN-γ and granzyme B production. viSNE and SPADE profiling identified overlapping and distinct IFN-γ+ and GZMB+ subsets. The super-antigenic properties of P3 were further evident by its selective expansion of T-cells expressing specific TCR Vα and Vβ chain repertoires. In vivo experiments in mice revealed that the administration of P3 led to a significant upregulation of proinflammatory cytokines IL-1β, IL-6, and TNF-α. While the clinical significance of P3 in COVID-19 remains unclear, its homology to other mammalian proteins suggests a potential role for this peptide family in human inflammation and autoimmunity.","journal":"Communications Biology","year":2025,"id":516805,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"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":1382708,"name":"Fatima Ezzahra Bennani","orcid":"0000-0003-0981-3959","position":1,"is_corresponding":false},{"id":1382709,"name":"Nasser Masroori","orcid":"0000-0002-5825-1406","position":2,"is_corresponding":false},{"id":1382710,"name":"Chen Liu","orcid":"0000-0002-5693-8634","position":3,"is_corresponding":false},{"id":1383198,"name":"Atena Nemati","orcid":null,"position":4,"is_corresponding":false},{"id":1382711,"name":"Nicholas Rozza","orcid":"0000-0003-1713-8949","position":5,"is_corresponding":false},{"id":1382712,"name":"Ami Grunbaum","orcid":"0000-0001-8745-0036","position":6,"is_corresponding":false},{"id":661319,"name":"Richard Kremer","orcid":"0000-0002-7053-2139","position":7,"is_corresponding":false},{"id":1383199,"name":"Catalin Milhalcioiu","orcid":null,"position":8,"is_corresponding":false},{"id":477609,"name":"Denis‐Claude Roy","orcid":"0000-0002-5921-1692","position":9,"is_corresponding":false},{"id":608918,"name":"Christopher E. Rudd","orcid":"0000-0001-5295-9019","position":10,"is_corresponding":false},{"id":1382707,"name":"Thai Hien Tu","orcid":"0000-0002-6674-012X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:48:54.768083Z","pmid":"39762551","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":[]}