{"doi":"10.21417/ac2020eji","title":"Broadly reactive human CD4 + T cells against Enterobacteriaceae are found in the naïve repertoire and are clonally expanded in the memory repertoire","abstract":"Enterobacteriaceae are a large family of Gram-negative bacteria that includes both commensals and opportunistic pathogens. The latter can cause severe nosocomial infections, with outbreaks of multi-antibiotics resistant strains, thus being a major public health threat. In this study, we report that Enterobacteriaceae-reactive memory Th cells were highly enriched in a CCR6+ CXCR3+ Th1*/17 cell subset and produced IFN-γ, IL-17A, and IL-22. This T cell subset was severely reduced in septic patients with K. pneumoniae bloodstream infection who also selectively lacked circulating K. pneumonie-reactive T cells. By combining heterologous antigenic stimulation, single cell cloning and TCR Vβ sequencing, we demonstrate that a large fraction of memory Th cell clones was broadly cross-reactive to several Enterobacteriaceae species. These cross-reactive Th cell clones were expanded in vivo and a large fraction of them recognized the conserved outer membrane protein A antigen. Interestingly, Enterobacteriaceae broadly cross-reactive T cells were also prominent among in vitro primed naïve T cells. Collectively, these data point to the existence of immunodominant T cell epitopes shared among different Enterobacteriaceae species and targeted by cross-reactive T cells that are readily found in the pre-immune repertoire and are clonally expanded in the memory repertoire.","journal":"immuneACCESS","year":2021,"id":222546,"datarank":0.1395781059856112,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.035606028901619416,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.035606028901619416,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":823829,"name":"JD Goldstein","orcid":null,"position":1,"is_corresponding":false},{"id":823830,"name":"G Durini","orcid":null,"position":2,"is_corresponding":false},{"id":823831,"name":"D Jarrossay","orcid":null,"position":3,"is_corresponding":false},{"id":823832,"name":"FB Menozzi","orcid":null,"position":4,"is_corresponding":false},{"id":823833,"name":"M Venditti","orcid":null,"position":5,"is_corresponding":false},{"id":823834,"name":"A Russo","orcid":null,"position":6,"is_corresponding":false},{"id":823835,"name":"M Falcone","orcid":null,"position":7,"is_corresponding":false},{"id":823836,"name":"A Lanzavecchia","orcid":null,"position":8,"is_corresponding":false},{"id":823837,"name":"MC Gagliardi","orcid":null,"position":9,"is_corresponding":false},{"id":823838,"name":"D Latorre","orcid":null,"position":10,"is_corresponding":false},{"id":73799,"name":"Federica Sallusto","orcid":"0000-0003-3750-2752","position":11,"is_corresponding":false},{"id":823828,"name":"A Cassotta","orcid":null,"position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:03.549854Z","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":[]}