{"doi":"10.3389/fimmu.2023.1182504","title":"Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4+ T-cell response with pre-primed responses directed against common cold coronaviruses","abstract":"Introduction The nonstructural protein 12 (NSP12) of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has a high sequence identity with common cold coronaviruses (CCC). Methods Here, we comprehensively assessed the breadth and specificity of the NSP12-specific T-cell response after in vitro T-cell expansion with 185 overlapping 15-mer peptides covering the entire SARS-CoV-2 NSP12 at single-peptide resolution in a cohort of 27 coronavirus disease 2019 (COVID-19) patients. Samples of nine uninfected seronegative individuals, as well as five pre-pandemic controls, were also examined to assess potential cross-reactivity with CCCs. Results Surprisingly, there was a comparable breadth of individual NSP12 peptide-specific CD4 + T-cell responses between COVID-19 patients (mean: 12.82 responses; range: 0–25) and seronegative controls including pre-pandemic samples (mean: 12.71 responses; range: 0–21). However, the NSP12-specific T-cell responses detected in acute COVID-19 patients were on average of a higher magnitude. The most frequently detected CD4 + T-cell peptide specificities in COVID-19 patients were aa236–250 (37%) and aa246–260 (44%), whereas the peptide specificities aa686–700 (50%) and aa741–755 (36%), were the most frequently detected in seronegative controls. In CCC-specific peptide-expanded T-cell cultures of seronegative individuals, the corresponding SARS-CoV-2 NSP12 peptide specificities also elicited responses in vitro . However, the NSP12 peptide-specific CD4 + T-cell response repertoire only partially overlapped in patients analyzed longitudinally before and after a SARS-CoV-2 infection. Discussion The results of the current study indicate the presence of pre-primed, cross-reactive CCC-specific T-cell responses targeting conserved regions of SARS-CoV-2, but they also underline the complexity of the analysis and the limited understanding of the role of the SARS-CoV-2 specific T-cell response and cross-reactivity with the CCCs.","journal":"Frontiers in Immunology","year":2023,"id":360685,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1112934,"name":"Maria Mader","orcid":null,"position":1,"is_corresponding":false},{"id":663700,"name":"Hendrik Karsten","orcid":"0000-0002-2767-0405","position":2,"is_corresponding":false},{"id":960406,"name":"Leon Cords","orcid":"0000-0003-1340-8817","position":3,"is_corresponding":false},{"id":960407,"name":"Maximilian Knapp","orcid":"0000-0002-9554-5067","position":4,"is_corresponding":false},{"id":664294,"name":"Sophia Schulte","orcid":null,"position":5,"is_corresponding":false},{"id":1112485,"name":"Lennart Hermanussen","orcid":"0000-0002-1800-1568","position":6,"is_corresponding":false},{"id":663701,"name":"Sven Peine","orcid":"0000-0002-6365-9916","position":7,"is_corresponding":false},{"id":1112935,"name":"Vanessa Ditt","orcid":null,"position":8,"is_corresponding":false},{"id":292649,"name":"Alba Grifoni","orcid":"0000-0002-2209-5966","position":9,"is_corresponding":false},{"id":960409,"name":"Marylyn M. Addo","orcid":"0000-0003-2836-9224","position":10,"is_corresponding":false},{"id":571383,"name":"Samuel Huber","orcid":"0000-0001-9325-8227","position":11,"is_corresponding":false},{"id":55670,"name":"Alessandro Sette","orcid":"0000-0001-7013-2250","position":12,"is_corresponding":false},{"id":663703,"name":"Marc Lütgehetmann","orcid":"0000-0002-9468-7944","position":13,"is_corresponding":false},{"id":1112486,"name":"Sven Pischke","orcid":"0000-0003-3370-3274","position":14,"is_corresponding":false},{"id":281006,"name":"William W. Kwok","orcid":"0000-0003-4843-4599","position":15,"is_corresponding":false},{"id":55666,"name":"John Sidney","orcid":"0000-0002-0987-405X","position":16,"is_corresponding":false},{"id":449503,"name":"Julian Schulze zur Wiesch","orcid":"0000-0002-5033-1938","position":17,"is_corresponding":false},{"id":1112933,"name":"Tim Westphal","orcid":null,"position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:14:06.433417Z","pmid":"37215095","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":[]}