{"doi":"10.1101/2024.01.26.577489","title":"A general platform for targeting MHC-II antigens via a single loop","abstract":"Abstract Class-II major histocompatibility complexes (MHC-IIs) are central to the communications between CD4+ T cells and antigen presenting cells (APCs), but intrinsic structural features associated with MHC-II make it difficult to develop a general targeting system with high affinity and antigen specificity. Here, we introduce a protein platform, Targeted Recognition of Antigen-MHC Complex Reporter for MHC-II ( TRACeR-II ), to enable the rapid development of peptide-specific MHC-II binders. TRACeR-II has a small helical bundle scaffold and uses an unconventional mechanism to recognize antigens via a single loop. This unique antigen-recognition mechanism renders this platform highly versatile and amenable to direct structural modeling of the interactions with the antigen. We demonstrate that TRACeR-II binders can be rapidly evolved across multiple alleles, while computational protein design can produce specific binding sequences for a SARS-CoV-2 peptide of unknown complex structure. TRACeR-II sheds light on a simple and straightforward approach to address the MHC peptide targeting challenge, without relying on combinatorial selection on complementarity determining region (CDR) loops. It presents a promising basis for further exploration in immune response modulation as well as a broad range of theragnostic applications.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489829,"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":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":915730,"name":"Jingjia Liu","orcid":"0000-0002-6038-593X","position":1,"is_corresponding":false},{"id":260360,"name":"Kevin M. Jude","orcid":"0000-0002-3675-5136","position":2,"is_corresponding":false},{"id":488940,"name":"Xinbo Yang","orcid":"0000-0002-1755-1349","position":3,"is_corresponding":false},{"id":1334983,"name":"Ying Li","orcid":"0000-0002-4795-2610","position":4,"is_corresponding":false},{"id":739076,"name":"Braxton Bell","orcid":null,"position":5,"is_corresponding":false},{"id":411154,"name":"Hongli Yang","orcid":"0000-0002-3636-9219","position":6,"is_corresponding":false},{"id":1048610,"name":"Audrey Kassardjian","orcid":"0000-0001-5141-5132","position":7,"is_corresponding":false},{"id":1255149,"name":"Ali Mobedi","orcid":null,"position":8,"is_corresponding":false},{"id":323503,"name":"Udit Parekh","orcid":"0000-0002-6395-1781","position":9,"is_corresponding":false},{"id":625083,"name":"R. Andres Parra Sperberg","orcid":null,"position":10,"is_corresponding":false},{"id":331370,"name":"Jean‐Philippe Julien","orcid":"0000-0001-7602-3995","position":11,"is_corresponding":false},{"id":350837,"name":"Elizabeth Mellins","orcid":"0000-0003-2577-139X","position":12,"is_corresponding":false},{"id":218189,"name":"K. Christopher García","orcid":"0000-0001-9273-0278","position":13,"is_corresponding":false},{"id":317333,"name":"Po‐Ssu Huang","orcid":"0000-0002-7948-2895","position":14,"is_corresponding":false},{"id":1217723,"name":"Haotian Du","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:08:28.548530Z","pmid":"38352315","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":[]}