{"doi":"10.1101/2020.02.03.932848","title":"An unusual MHC molecule generates protective CD8+ T cell responses to chronic infection","abstract":"Abstract The CD8+ T cell response to the intracellular parasite Toxoplasma gondii varies dramatically between mouse strains, resulting in differences in control of the parasite. Protection in BALB/c mice can be attributed to an unusually strong and protective MHC-1 L d -restricted CD8+ T cell response directed against a peptide derived from the parasite antigen GRA6. The MHC-1 L d molecule has limited peptide binding compared to conventional MHC molecules such as K b or D b , which correlates with polymorphisms associated with “elite control” of HIV in humans. To investigate the link between the unusual MHC-1 molecule L d and the generation of “elite controller” CD8+ T cell responses, we compared the GRA6-L d specific T cell response to the well-studied OVA-K b specific response, and demonstrated that GRA6-L d specific T cells are significantly more protective and resistant to exhaustion in chronic T. gondii infection. To further investigate the connection between limited peptide presentation and robust T cell responses, we used CRISPR/Cas9 to generate mice with a point mutation (W97R) in the peptide-binding groove of L d that results in broader peptide binding. We investigated the effect of this L d W97R mutation on another robust L d -restricted response against the IE1 peptide during Murine Cytomegalovirus (MCMV) infection. This mutation leads to an increase in exhaustion markers in the IE1-L d specific CD8+ T cell response. Our results indicate that limited peptide binding by MHC-1 L d correlates with the development of robust and protective CD8+ T cell responses that may avoid exhaustion during chronic infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124576,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"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":400890,"name":"D.J. Bangs","orcid":null,"position":1,"is_corresponding":false},{"id":372450,"name":"Lydia K. Lutes","orcid":"0000-0001-6133-6294","position":2,"is_corresponding":false},{"id":570384,"name":"S.F. Chan","orcid":null,"position":3,"is_corresponding":false},{"id":569682,"name":"Kathrin Geiger","orcid":"0009-0005-1623-3938","position":4,"is_corresponding":false},{"id":499461,"name":"A Modzelewski","orcid":"0000-0003-0698-957X","position":5,"is_corresponding":false},{"id":235437,"name":"Lara Labarta-Bajo","orcid":"0000-0003-1812-6704","position":6,"is_corresponding":false},{"id":550966,"name":"Yan Wang","orcid":"0000-0003-0671-7312","position":7,"is_corresponding":false},{"id":569683,"name":"E.I. Zuniga","orcid":"0009-0005-0710-2469","position":8,"is_corresponding":false},{"id":455530,"name":"Shaodong Dai","orcid":"0000-0003-4760-2773","position":9,"is_corresponding":false},{"id":372451,"name":"Ellen A. Robey","orcid":"0000-0002-3630-5266","position":10,"is_corresponding":false},{"id":513522,"name":"Alexandra Tsitsiklis","orcid":"0000-0003-3467-1171","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-18T23:15:11.632153Z","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":[]}