{"doi":"10.3389/fimmu.2022.886683","title":"Identification of Highly Cross-Reactive Mimotopes for a Public T Cell Response in Murine Melanoma","abstract":"While immune checkpoint blockade results in durable responses for some patients, many others have not experienced such benefits. These treatments rely upon reinvigorating specific T cell-antigen interactions. However, it is often unknown what antigens are being recognized by T cells or how to potently induce antigen-specific responses in a broadly applicable manner. Here, we characterized the CD8 + T cell response to a murine model of melanoma following combination immunotherapy to determine the basis of tumor recognition. Sequencing of tumor-infiltrating T cells revealed a repertoire of highly homologous TCR sequences that were particularly expanded in treated mice and which recognized an antigen from an endogenous retrovirus. While vaccination against this peptide failed to raise a protective T cell response in vivo , engineered antigen mimotopes induced a significant expansion of CD8 + T cells cross-reactive to the original antigen. Vaccination with mimotopes resulted in killing of antigen-loaded cells in vivo yet showed modest survival benefit in a prophylactic vaccine paradigm. Together, this work demonstrates the identification of a dominant tumor-associated antigen and generation of mimotopes which can induce robust functional T cell responses that are cross-reactive to the endogenous antigen across multiple individuals.","journal":"Frontiers in Immunology","year":2022,"id":261047,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":915246,"name":"Coralie M. 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Dobson","orcid":"0000-0001-6486-536X","position":9,"is_corresponding":false},{"id":54219,"name":"Taeyoon Kyung","orcid":null,"position":10,"is_corresponding":false},{"id":54223,"name":"Khloe S. Gordon","orcid":"0000-0003-3652-7245","position":11,"is_corresponding":false},{"id":560675,"name":"Patrick V. Holec","orcid":"0000-0003-2342-7616","position":12,"is_corresponding":false},{"id":670953,"name":"Overbeck C. Takou Mbah","orcid":"0000-0003-3059-421X","position":13,"is_corresponding":false},{"id":915248,"name":"Daniel Garafola","orcid":"0000-0002-2931-3663","position":14,"is_corresponding":false},{"id":859266,"name":"Shengwei Wu","orcid":"0000-0003-1127-3330","position":15,"is_corresponding":false},{"id":63891,"name":"John Christopher Love","orcid":"0000-0003-0921-3144","position":16,"is_corresponding":false},{"id":314110,"name":"K. Dane Wittrup","orcid":"0000-0003-2398-5896","position":17,"is_corresponding":false},{"id":236278,"name":"Darrell J. 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