{"doi":"10.1016/j.celrep.2023.113410","title":"Stringent and complex sequence constraints of an IGHV1-69 broadly neutralizing antibody to influenza HA stem","abstract":"IGHV1-69 is frequently utilized by broadly neutralizing influenza antibodies to the hemagglutinin (HA) stem. These IGHV1-69 HA stem antibodies have diverse complementarity-determining region (CDR) H3 sequences. Besides, their light chains have minimal to no contact with the epitope. Consequently, sequence determinants that confer IGHV1-69 antibodies with HA stem specificity remain largely elusive. Using high-throughput experiments, this study reveals the importance of light-chain sequence for the IGHV1-69 HA stem antibody CR9114, which is the broadest influenza antibody known to date. Moreover, we demonstrate that the CDR H3 sequences from many other IGHV1-69 antibodies, including those to the HA stem, are incompatible with CR9114. Along with mutagenesis and structural analysis, our results indicate that light-chain and CDR H3 sequences coordinately determine the HA stem specificity of IGHV1-69 antibodies. Overall, this work provides molecular insights into broadly neutralizing antibody responses to influenza virus, which have important implications for universal influenza vaccine development.","journal":"Cell Reports","year":2023,"id":351986,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"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":0.9493,"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":228189,"name":"Yiquan Wang","orcid":"0000-0002-1954-9808","position":1,"is_corresponding":false},{"id":105428,"name":"Huibin Lv","orcid":"0000-0003-2218-0076","position":2,"is_corresponding":false},{"id":552629,"name":"Timothy J.C. Tan","orcid":"0000-0001-5337-5357","position":3,"is_corresponding":false},{"id":688066,"name":"Ruipeng Lei","orcid":"0000-0002-4652-3400","position":4,"is_corresponding":false},{"id":1097522,"name":"Kevin J. Mao","orcid":null,"position":5,"is_corresponding":false},{"id":105424,"name":"Nicholas C. Wu","orcid":"0000-0002-9078-6697","position":6,"is_corresponding":false},{"id":630593,"name":"Qi Wen Teo","orcid":"0000-0001-6749-9684","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:12:45.897709Z","pmid":"37976161","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":[]}