{"doi":"10.1016/j.cell.2023.10.024","title":"TScan-II: A genome-scale platform for the de novo identification of CD4+ T cell epitopes","abstract":"CD4 + T cells play fundamental roles in orchestrating immune responses and tissue homeostasis. However, our inability to associate peptide human leukocyte antigen class-II (HLA-II) complexes with their cognate T cell receptors (TCRs) in an unbiased manner has hampered our understanding of CD4 + T cell function and role in pathologies. Here, we introduce TScan-II, a highly sensitive genome-scale CD4 + antigen discovery platform. This platform seamlessly integrates the endogenous HLA-II antigen-processing machinery in synthetic antigen-presenting cells and TCR signaling in T cells, enabling the simultaneous screening of multiple HLAs and TCRs. Leveraging genome-scale human, virome, and epitope mutagenesis libraries, TScan-II facilitates de novo antigen discovery and deep exploration of TCR specificity. We demonstrate TScan-II's potential for basic and translational research by identifying a non-canonical antigen for a cancer-reactive CD4 + T cell clone. Additionally, we identified two antigens for clonally expanded CD4 + T cells in Sjögren's disease, which bind distinct HLAs and are expressed in HLA-II-positive ductal cells within affected salivary glands.","journal":"Cell","year":2023,"id":319819,"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":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9295,"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":108412,"name":"Tomasz Kula","orcid":"0000-0002-6458-9833","position":1,"is_corresponding":false},{"id":551798,"name":"Thomas Pranzatelli","orcid":"0000-0002-5763-1036","position":2,"is_corresponding":false},{"id":16695,"name":"Nolan Kamitaki","orcid":"0000-0003-0614-0189","position":3,"is_corresponding":false},{"id":1030226,"name":"Qingda Meng","orcid":null,"position":4,"is_corresponding":false},{"id":281374,"name":"Bhuwan Khatri","orcid":"0000-0001-5456-2963","position":5,"is_corresponding":false},{"id":298799,"name":"Paola Pérez","orcid":"0000-0002-1695-5763","position":6,"is_corresponding":false},{"id":615643,"name":"Qikai Xu","orcid":"0000-0003-0622-0998","position":7,"is_corresponding":false},{"id":618175,"name":"Aiquan Chang","orcid":"0000-0002-9482-0979","position":8,"is_corresponding":false},{"id":85071,"name":"Ayano C. Kohlgruber","orcid":"0000-0001-6758-3966","position":9,"is_corresponding":false},{"id":108415,"name":"Yumei Leng","orcid":"0000-0003-2512-9284","position":10,"is_corresponding":false},{"id":1030227,"name":"Ananth Aditya Jupudi","orcid":null,"position":11,"is_corresponding":false},{"id":494941,"name":"Michelle L. Joachims","orcid":null,"position":12,"is_corresponding":false},{"id":242306,"name":"John A. Chiorini","orcid":"0000-0003-4919-4056","position":13,"is_corresponding":false},{"id":281380,"name":"Christopher J. Lessard","orcid":"0000-0003-2440-3843","position":14,"is_corresponding":false},{"id":419781,"name":"A. Darise Farris","orcid":"0000-0003-3009-2017","position":15,"is_corresponding":false},{"id":51552,"name":"Senthil K. Muthuswamy","orcid":"0000-0001-6564-9634","position":16,"is_corresponding":false},{"id":298802,"name":"Blake M. Warner","orcid":"0000-0002-4961-018X","position":17,"is_corresponding":false},{"id":108430,"name":"Stephen J. Elledge","orcid":"0000-0001-7923-6283","position":18,"is_corresponding":false},{"id":1029570,"name":"M Dezfulian","orcid":"0000-0001-9979-5365","position":0,"is_corresponding":true}],"reference_count":117,"raw_metadata":null,"created_at":"2026-07-19T01:07:17.361058Z","pmid":"38016469","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":[]}