{"doi":"10.4049/jimmunol.174.6.3352","title":"Amelioration of Established Experimental Autoimmune Encephalomyelitis by an MHC Anchor-Substituted Variant of Proteolipid Protein 139–151","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Murine experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated autoimmune disorder directed against myelin proteins within the CNS. We propose that variant peptides containing amino acid substitutions at MHC anchor residues will provide a unique means to controlling the polyclonal autoimmune T cell response. In this study, we have identified an MHC variant of proteolipid protein (PLP) 139–151 (145D) that renders PLP139–151-specific T cell lines anergic in vitro, as defined by a significant reduction in proliferation and IL-2 production following challenge with wild-type peptide. In vivo administration of 145D before challenge with PLP139–151 results in a significant reduction in disease severity and incidence. Importantly, we demonstrate the ability of an MHC variant peptide to ameliorate established EAE. An advantage to this treatment is that the MHC variant peptide does not induce an acute hypersensitivity reaction. This is in contrast to previous work in the PLP139–151 model demonstrating that anaphylactic shock resulting in death occurs upon rechallenge with the encephalitogenic peptide. Taken together, these data demonstrate the effectiveness of MHC anchor-substituted peptides in the treatment of EAE and suggest their utility in the treatment of other autoimmune disorders.</jats:p>","journal":"The Journal of Immunology","year":2005,"id":686129,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1792576,"name":"Mandy L Ford","orcid":null,"position":1,"is_corresponding":false},{"id":1792577,"name":"Brian D Evavold","orcid":null,"position":2,"is_corresponding":false},{"id":1792575,"name":"Carrie D Margot","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Amelioration of Established Experimental Autoimmune Encephalomyelitis by an MHC Anchor-Substituted Variant of Proteolipid Protein 139–151","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Murine experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated autoimmune disorder directed against myelin proteins within the CNS. We propose that variant peptides containing amino acid substitutions at MHC anchor residues will provide a unique means to controlling the polyclonal autoimmune T cell response. In this study, we have identified an MHC variant of proteolipid protein (PLP) 139–151 (145D) that renders PLP139–151-specific T cell lines anergic in vitro, as defined by a significant reduction in proliferation and IL-2 production following challenge with wild-type peptide. In vivo administration of 145D before challenge with PLP139–151 results in a significant reduction in disease severity and incidence. Importantly, we demonstrate the ability of an MHC variant peptide to ameliorate established EAE. An advantage to this treatment is that the MHC variant peptide does not induce an acute hypersensitivity reaction. This is in contrast to previous work in the PLP139–151 model demonstrating that anaphylactic shock resulting in death occurs upon rechallenge with the encephalitogenic peptide. Taken together, these data demonstrate the effectiveness of MHC anchor-substituted peptides in the treatment of EAE and suggest their utility in the treatment of other autoimmune disorders.</jats:p>","is_dataset_classified":null,"base_score":3.332204510175204,"endowment":3.332204510175204,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15749867","pmcid":null,"openalex_id":"https://openalex.org/W1918574950","authors":[],"funders":[],"total_grants":0,"fwci":1.0304,"citation_percentile":0.74165652,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":2},{"year":2014,"count":2},{"year":2015,"count":2},{"year":2024,"count":1}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/174/6/3352/1198836/3352.pdf","host_type":"journal"},{"url":"https://journals.aai.org/jimmunol/article-pdf/174/6/3352/1198836/3352.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/174/6/3352/62615368/3352.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.174.6.3352","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15749867","host_type":"repository"}],"fields_of_study":["Immune Cell Function and Interaction","T-cell and B-cell Immunology","Immunotherapy and Immune Responses","Amino Acid Sequence","Amino Acid Substitution","Animals","Cell Line","Clonal Anergy","Encephalomyelitis, Autoimmune, Experimental","Female","Genetic Variation","Immunization","Immunotherapy","In Vitro Techniques","Major Histocompatibility Complex","Mice","Myelin Proteolipid Protein","Peptide Fragments","T-Lymphocytes"],"mesh_terms":["Amino Acid Sequence","Animals","Cell Line","Encephalomyelitis, Autoimmune, Experimental","Female","Immunization","Immunotherapy","Major Histocompatibility Complex","Peptide Fragments","T-Lymphocytes","Genetic Variation","Clonal Anergy","Myelin Proteolipid Protein","Amino Acid Substitution","Mice","In Vitro Techniques"],"keywords":["Experimental autoimmune encephalomyelitis","Proteolipid protein 1","Myelin proteolipid protein","Biology","Immunology","Myelin basic protein","Major histocompatibility complex","T cell","Multiple sclerosis","Peptide","Myelin","Autoimmune disease","Antigen","Immune system","Biochemistry","Central nervous system","Neuroscience","Antibody"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T18:36:11.093702Z","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":[]}