{"doi":"10.1083/jcb.201905085","title":"PD-1 and BTLA regulate T cell signaling differentially and only partially through SHP1 and SHP2","abstract":"Blockade antibodies of the immunoinhibitory receptor PD-1 can stimulate the anti-tumor activity of T cells, but clinical benefit is limited to a fraction of patients. Evidence suggests that BTLA, a receptor structurally related to PD-1, may contribute to resistance to PD-1 targeted therapy, but how BTLA and PD-1 differ in their mechanisms is debated. Here, we compared the abilities of BTLA and PD-1 to recruit effector molecules and to regulate T cell signaling. While PD-1 selectively recruited SHP2 over the stronger phosphatase SHP1, BTLA preferentially recruited SHP1 to more efficiently suppress T cell signaling. Contrary to the dominant view that PD-1 and BTLA signal exclusively through SHP1/2, we found that in SHP1/2 double-deficient primary T cells, PD-1 and BTLA still potently inhibited cell proliferation and cytokine production, albeit more transiently than in wild type T cells. Thus, PD-1 and BTLA can suppress T cell signaling through a mechanism independent of both SHP1 and SHP2.","journal":"The Journal of Cell Biology","year":2020,"id":53358,"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":118,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271871,"name":"Bowen Hou","orcid":"0000-0002-1974-8938","position":1,"is_corresponding":false},{"id":271872,"name":"Amitkumar Fulzele","orcid":"0000-0003-1255-6981","position":2,"is_corresponding":false},{"id":271873,"name":"Takeya Masubuchi","orcid":"0000-0001-6822-3049","position":3,"is_corresponding":false},{"id":271874,"name":"Yunlong Zhao","orcid":"0000-0002-7392-4824","position":4,"is_corresponding":false},{"id":271875,"name":"Zijun Wu","orcid":"0000-0001-5020-5619","position":5,"is_corresponding":false},{"id":271876,"name":"Yanyan Hu","orcid":"0000-0002-5401-4980","position":6,"is_corresponding":false},{"id":271877,"name":"Yong Jiang","orcid":"0000-0002-0163-5089","position":7,"is_corresponding":false},{"id":273137,"name":"Yanzhe Ma","orcid":null,"position":8,"is_corresponding":false},{"id":271878,"name":"Haopeng Wang","orcid":"0000-0002-4995-0838","position":9,"is_corresponding":false},{"id":248001,"name":"Eric J. Bennett","orcid":"0000-0002-1201-3314","position":10,"is_corresponding":false},{"id":271879,"name":"Guo Fu","orcid":"0000-0001-5451-5219","position":11,"is_corresponding":false},{"id":271880,"name":"Enfu Hui","orcid":"0000-0001-7876-2783","position":12,"is_corresponding":false},{"id":271870,"name":"Xiaozheng Xu","orcid":"0000-0001-6888-4285","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T20:44:25.349797Z","pmid":"32437509","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":[]}