{"doi":"10.1093/protein/gzab034","title":"Immortalization and functional screening of natively paired human T cell receptor repertoires","abstract":"Functional analyses of the T cell receptor (TCR) landscape can reveal critical information about protection from disease and molecular responses to vaccines. However, it has proven difficult to combine advanced next-generation sequencing technologies with methods to decode the peptide-major histocompatibility complex (pMHC) specificity of individual TCRs. We developed a new high-throughput approach to enable repertoire-scale functional evaluations of natively paired TCRs. In particular, we leveraged the immortalized nature of physically linked TCRα:β amplicon libraries to analyze binding against multiple recombinant pMHCs on a repertoire scale, and to exemplify the utility of this approach, we also performed affinity-based functional mapping in conjunction with quantitative next-generation sequencing to track antigen-specific TCRs. These data successfully validated a new immortalization and screening platform to facilitate detailed molecular analyses of disease-relevant antigen interactions with human TCRs.","journal":"Protein Engineering Design and Selection","year":2021,"id":183760,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"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":738120,"name":"Cheng-Yu Chung","orcid":null,"position":1,"is_corresponding":false},{"id":302418,"name":"Sheila N. López Acevedo","orcid":"0000-0003-2778-4696","position":2,"is_corresponding":false},{"id":738121,"name":"Nicoleen Boyle","orcid":null,"position":3,"is_corresponding":false},{"id":302419,"name":"Bharat Madan","orcid":"0000-0002-7376-9991","position":4,"is_corresponding":false},{"id":236781,"name":"Matías Gutiérrez-González","orcid":"0000-0002-9729-6850","position":5,"is_corresponding":false},{"id":290823,"name":"Rodrigo Matus‐Nicodemos","orcid":"0000-0003-3676-4312","position":6,"is_corresponding":false},{"id":655413,"name":"Amy D. Laflin","orcid":"0000-0003-2571-2824","position":7,"is_corresponding":false},{"id":738122,"name":"Rukmini Ladi","orcid":null,"position":8,"is_corresponding":false},{"id":737622,"name":"John Zhou","orcid":"0000-0002-9515-0161","position":9,"is_corresponding":false},{"id":302422,"name":"Jacy R. Wolfe","orcid":"0000-0001-5206-4135","position":10,"is_corresponding":false},{"id":104830,"name":"Sian Llewellyn‐Lacey","orcid":"0000-0002-4703-0413","position":11,"is_corresponding":false},{"id":290824,"name":"Richard A. Koup","orcid":"0000-0002-3090-7282","position":12,"is_corresponding":false},{"id":277153,"name":"Daniel C. Douek","orcid":"0000-0001-5575-8634","position":13,"is_corresponding":false},{"id":738123,"name":"Henry H. Balfour","orcid":null,"position":14,"is_corresponding":false},{"id":104895,"name":"David A. Price","orcid":"0000-0001-9416-2737","position":15,"is_corresponding":false},{"id":108827,"name":"Brandon J. DeKosky","orcid":"0000-0001-6406-0836","position":16,"is_corresponding":false},{"id":302417,"name":"Ahmed S. Fahad","orcid":"0000-0002-5088-9333","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:48:22.008011Z","pmid":"35174859","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":[]}