{"doi":"10.1101/2021.03.04.433914","title":"High-Throughput and High-Dimensional Single Cell Analysis of Antigen-Specific CD8 <sup>+</sup> T cells","abstract":"Abstract Although critical to T cell function, antigen specificity is often omitted in high-throughput multi-omics based T cell profiling due to technical challenges. We describe a high-dimensional, tetramer-associated T cell receptor sequencing (TetTCR-SeqHD) method to simultaneously profile TCR sequences, cognate antigen specificities, targeted gene-expression, and surface-protein expression from tens of thousands of single cells. Using polyclonal CD8 + T cells with known antigen specificity and TCR sequences, we demonstrated over 98% precision for detecting the correct antigen specificity. We also evaluated gene-expression and phenotypic differences among antigen-specific CD8 + T cells and characterized phenotype signatures of influenza- and EBV-specific CD8 + T cells that are unique to their pathogen targets. Moreover, with the high-throughput capacity of profiling hundreds of antigens simultaneously, we applied TetTCR-SeqHD to identify antigens that preferentially enrich cognate CD8 + T cells in type 1 diabetes patients compared to healthy controls, and discovered a TCR that cross reacts between diabetic and microbiome antigens. TetTCR-SeqHD is a powerful approach for profiling T cell responses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":218472,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9221,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"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":641550,"name":"Alexandra A. Schonnesen","orcid":null,"position":1,"is_corresponding":false},{"id":447557,"name":"Chenfeng He","orcid":"0000-0002-9171-3879","position":2,"is_corresponding":false},{"id":640979,"name":"Amanda Y. Xia","orcid":"0000-0002-3344-7699","position":3,"is_corresponding":false},{"id":640980,"name":"Eric Sun","orcid":"0000-0002-2810-929X","position":4,"is_corresponding":false},{"id":640981,"name":"Eunise Chen","orcid":"0009-0005-2203-8258","position":5,"is_corresponding":false},{"id":641551,"name":"Katherine Sebastian","orcid":null,"position":6,"is_corresponding":false},{"id":65553,"name":"Robert Balderas","orcid":"0000-0002-8734-8629","position":7,"is_corresponding":false},{"id":641553,"name":"Mrinalini Kulkarni-Date","orcid":null,"position":8,"is_corresponding":false},{"id":262878,"name":"Ning Jiang","orcid":"0000-0003-1103-5922","position":9,"is_corresponding":false},{"id":640978,"name":"Ke-Yue Ma","orcid":"0000-0003-2953-3700","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:53:29.626149Z","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":[]}