{"doi":"10.1126/sciimmunol.ade6256","title":"Transmembrane domain–driven PD-1 dimers mediate T cell inhibition","abstract":"Programmed cell death-1 (PD-1) is a potent immune checkpoint receptor on T lymphocytes. Upon engagement by its ligands, PD-L1 or PD-L2, PD-1 inhibits T cell activation and can promote immune tolerance. Antagonism of PD-1 signaling has proven effective in cancer immunotherapy, and conversely, agonists of the receptor may have a role in treating autoimmune disease. Some immune receptors function as dimers, but PD-1 has been considered monomeric. Here, we show that PD-1 and its ligands form dimers as a consequence of transmembrane domain interactions and that propensity for dimerization correlates with the ability of PD-1 to inhibit immune responses, antitumor immunity, cytotoxic T cell function, and autoimmune tissue destruction. These observations contribute to our understanding of the PD-1 axis and how it can potentially be manipulated for improved treatment of cancer and autoimmune diseases.","journal":"Science Immunology","year":2024,"id":419093,"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":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9456,"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":949433,"name":"Jia Liu","orcid":"0000-0003-3612-6089","position":1,"is_corresponding":false},{"id":857282,"name":"Audun Kvalvaag","orcid":"0000-0002-6437-2247","position":2,"is_corresponding":false},{"id":1208358,"name":"Alexander M. Mørch","orcid":"0000-0002-1881-2424","position":3,"is_corresponding":false},{"id":653993,"name":"Anna S. Tocheva","orcid":"0000-0002-3327-0811","position":4,"is_corresponding":false},{"id":649381,"name":"Charles Ng","orcid":"0000-0003-3696-1498","position":5,"is_corresponding":false},{"id":1208359,"name":"Hong Liang","orcid":"0009-0004-1274-4661","position":6,"is_corresponding":false},{"id":770714,"name":"Ian M. Ahearn","orcid":"0000-0002-2275-137X","position":7,"is_corresponding":false},{"id":1038099,"name":"Ruimin Pan","orcid":"0000-0002-6947-1658","position":8,"is_corresponding":false},{"id":28987,"name":"Christina C. Luo","orcid":"0000-0001-9872-7432","position":9,"is_corresponding":false},{"id":1208360,"name":"Alexander Leithner","orcid":"0000-0002-1073-744X","position":10,"is_corresponding":false},{"id":1208361,"name":"Zhihua Qin","orcid":"0000-0003-3195-7641","position":11,"is_corresponding":false},{"id":302566,"name":"Yong Zhou","orcid":"0000-0002-0214-8151","position":12,"is_corresponding":false},{"id":1050884,"name":"Antonio García‐España","orcid":"0000-0002-9957-3161","position":13,"is_corresponding":false},{"id":382487,"name":"Adam Mor","orcid":"0000-0002-2854-2405","position":14,"is_corresponding":false},{"id":90201,"name":"Dan R. Littman","orcid":"0000-0002-2850-8688","position":15,"is_corresponding":false},{"id":61554,"name":"Michael L. Dustin","orcid":"0000-0003-4983-6389","position":16,"is_corresponding":false},{"id":231017,"name":"Jun Wang","orcid":"0000-0002-6346-2929","position":17,"is_corresponding":false},{"id":228625,"name":"Xiang‐Peng Kong","orcid":"0000-0001-5773-2681","position":18,"is_corresponding":false},{"id":1208357,"name":"Elliot A. Philips","orcid":"0000-0002-6407-1890","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:57:14.586331Z","pmid":"38457513","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":[]}