{"doi":"10.4049/jimmunol.2000340","title":"Conditional Silencing of H-2Db Class I Molecule Expression Modulates the Protective and Pathogenic Kinetics of Virus-Antigen–Specific CD8 T Cell Responses during Theiler's Virus Infection","abstract":"Abstract Theiler's murine encephalomyelitis virus (TMEV) infection of the CNS is cleared in C57BL/6 mice by a CD8 T cell response restricted by the MHC class I molecule H-2Db. The identity and function of the APC(s) involved in the priming of this T cell response is (are) poorly defined. To address this gap in knowledge, we developed an H-2Db LoxP-transgenic mouse system using otherwise MHC class I–deficient C57BL/6 mice, thereby conditionally ablating MHC class I–restricted Ag presentation in targeted APC subpopulations. We observed that CD11c+ APCs are critical for early priming of CD8 T cells against the immunodominant TMEV peptide VP2121-130. Loss of H-2Db on CD11c+ APCs mitigates the CD8 T cell response, preventing early viral clearance and immunopathology associated with CD8 T cell activity in the CNS. In contrast, animals with H-2Db–deficient LysM+ APCs retained early priming of Db:VP2121-130 epitope–specific CD8 T cells, although a modest reduction in immune cell entry into the CNS was observed. This work establishes a model enabling the critical dissection of H-2Db–restricted Ag presentation to CD8 T cells, revealing cell-specific and temporal features involved in the generation of CD8 T cell responses. Employing this novel system, we establish CD11c+ cells as pivotal to the establishment of acute antiviral CD8 T cell responses against the TMEV immunodominant epitope VP2121-130, with functional implications both for T cell–mediated viral control and immunopathology.","journal":"The Journal of Immunology","year":2020,"id":81295,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"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":420496,"name":"Robin C. Orozco","orcid":"0000-0002-2138-2912","position":1,"is_corresponding":false},{"id":420497,"name":"Courtney S. Malo","orcid":"0000-0001-9674-3826","position":2,"is_corresponding":false},{"id":256583,"name":"Katayoun Ayasoufi","orcid":"0000-0002-3797-0823","position":3,"is_corresponding":false},{"id":281060,"name":"Cori E. Fain","orcid":"0000-0002-8323-6419","position":4,"is_corresponding":false},{"id":283349,"name":"Roman H. Khadka","orcid":null,"position":5,"is_corresponding":false},{"id":281059,"name":"Emma N. Goddery","orcid":"0000-0001-6632-8226","position":6,"is_corresponding":false},{"id":281061,"name":"Lila T. Yokanovich","orcid":"0000-0002-3823-4051","position":7,"is_corresponding":false},{"id":274116,"name":"Megan L. Settell","orcid":"0000-0002-2924-360X","position":8,"is_corresponding":false},{"id":281064,"name":"Michael J. Hansen","orcid":"0000-0001-7712-0375","position":9,"is_corresponding":false},{"id":281063,"name":"Fang Jin","orcid":"0000-0001-5188-5206","position":10,"is_corresponding":false},{"id":230194,"name":"Kevin D. Pavelko","orcid":"0000-0001-7555-1315","position":11,"is_corresponding":false},{"id":61839,"name":"Larry R. Pease","orcid":"0000-0001-9770-1740","position":12,"is_corresponding":false},{"id":256585,"name":"Aaron J. Johnson","orcid":"0000-0002-7921-484X","position":13,"is_corresponding":false},{"id":281058,"name":"Zachariah P. Tritz","orcid":"0000-0002-5836-7839","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T21:52:34.401799Z","pmid":"32737149","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":[]}