{"doi":"10.4049/jimmunol.210.supp.169.15","title":"Inhibition of TCR-MHC-II interactions abrogates Treg-mediated immune suppression and augments anti-tumor immunity","abstract":"Abstract CD4+Foxp3+ Tregs play a non-redundant role in controlling autoimmunity. Continuous TCR signaling and the availability of exogenous IL-2 from CD4+ effectors regulate the size of the Treg pool and their suppressive function in the steady state. Homeostatic proliferation of Tregs and memory phenotype (MP) CD4+Foxp3−T cells depends on CD80/CD86-CD28 signaling. Acute blockade of TCR-MHC-II interactions in vivo by anti-MHC-II mAb significantly enhances memory phenotype (MP) Treg, CD4+, and CD8+ T cell expansion by a CD28-dependent pathway. IL-15 trans presentation by APC also contributes to Treg, MP CD4+ and MP CD8+ proliferation following blockade of TCR-MHC-II interaction by a CD122-dependent pathway. Combined CD28 activation and IL-15 stimulation together with IL-2 deprivation secondary to MHCII-TCR blockade result in decreased expression of CD25, but enhancement of Foxp3 expression by Treg. In addition, Treg exhibit decreased pAKT/NFAT signaling, but enhanced pSTAT5/mTOR signaling. Mice transplanted with several different transplantable tumors manifest enhanced tumor immunity in the presence of MHCII-TCR inhibition. Our results demonstrate that in the absence of TCR-MHC-II interactions, Treg proliferate, but lose their identity and manifest disabled suppressor function resulting in enhanced innate and adaptive immunity against cancer progression. This work was supported by the Intramural Research Program of NIAID, NIH. This work was supported by the Intramural Research Program of NIAID, NIH.","journal":"The Journal of Immunology","year":2023,"id":410199,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"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":321383,"name":"Ethan M. Shevach","orcid":"0000-0003-1607-4664","position":1,"is_corresponding":false},{"id":385520,"name":"Abir K. Panda","orcid":"0000-0002-8139-7016","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:21:31.144858Z","pmid":null,"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":[]}