{"doi":"10.1101/2020.05.11.088286","title":"Identification of antigen-specific TCR sequences using a strategy based on biological and statistical enrichment in unselected subjects","abstract":"Abstract Recent advances in high-throughput T cell receptor (TCR) sequencing have allowed for new insights into the TCR repertoire. However, methods for capturing antigen-specific repertoires remain an area of development. Here, we describe a novel approach that utilizes both a biological and statistical enrichment to define putatively antigen-specific complementarity-determining region 3 (CDR3) repertoires in unrelated individuals. The biological enrichment entails fluorescence-activated cell sorting of in vitro antigen-activated memory CD4 + T cells followed by TCRβ sequencing. The resulting TCRβ sequences are then filtered by selecting those that are statistically enriched when compared to their frequency in the autologous resting T cell compartment. Applying this method to define putatively peanut protein-specific repertoires in 27 peanut-allergic individuals resulted in a library of 7345 unique CDR3 amino acid sequences that had similar characteristics to validated antigen-specific repertoires in terms of homology and diversity. In-depth analysis of these CDR3s revealed 36 public sequences that demonstrated high levels of convergent recombination. In a network analysis, the public CDR3s unveiled themselves as core sequences with more edges than their private counterparts. This method has the potential to be applied to a wide range of T cell mediated disorders, and to yield new biomarkers and biological insights.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126662,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":490224,"name":"Bert Ruiter","orcid":"0000-0003-3945-3202","position":1,"is_corresponding":false},{"id":279470,"name":"Yamini V. Virkud","orcid":"0000-0001-7328-7215","position":2,"is_corresponding":false},{"id":254346,"name":"Wayne G. Shreffler","orcid":"0000-0001-6465-137X","position":3,"is_corresponding":false},{"id":89090,"name":"Neal P. Smith","orcid":"0000-0003-1394-3158","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","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":[]}