ArticleThe Journal of experimental medicine1996
Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus.
Article in The Journal of experimental medicine, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 212 citations in OpenAlex.
- Pathogenic drivers of lupus myocarditis and potential therapeutic targets.Experimental & molecular medicine · 2025Review
- Epitope Spreading in Immune-Mediated Glomerulonephritis: The Expanding Target.International journal of molecular sciences · 2024Review
- Vaccines for immune tolerance against autoimmune disease.Advanced drug delivery reviews · 2023Review
- The yin/yang balance of the MHC-selfFrontiers in immunology · 2022Review
- Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune rheumatic disease (AIRD).Clinical and experimental immunology · 2021Review
- Potential for Antigen-Specific Tolerizing Immunotherapy in Systematic Lupus Erythematosus.Frontiers in immunology · 2021Review
- Harnessing Tolerogenic Histone Peptide Epitopes From Nucleosomes for Selective Down-Regulation of Pathogenic Autoimmune Response in Lupus (Past, Present, and Future).Frontiers in immunology · 2021Review
- Regulation of the germinal center response by nuclear receptors and implications for autoimmune diseases.The FEBS journal · 2020Review
- Autoimmunity and SLE: Factual and Semantic Evidence-Based Critical Analyses of Definitions, Etiology, and Pathogenesis.Frontiers in immunology · 2020Review
- Anti-DNA antibodies--quintessential biomarkers of SLE.Nature reviews. Rheumatology · 2016Review
- Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity.The Journal of clinical investigation · 2015Review
- The effect of cell death in the initiation of lupus nephritis.Clinical and experimental immunology · 2015Review
- Major pathogenic steps in human lupus can be effectively suppressed by nucleosomal histone peptide epitope-induced regulatory immunity.Clinical immunology (Orlando, Fla.) · 2013Article
- Somatic mutagenesis in autoimmunity.Autoimmunity · 2013Review
- Autoantibodies in systemic lupus erythematosus.Pediatric nephrology (Berlin, Germany) · 2012Review
- Megakaryocyte progenitors are the main APCs inducing Th17 response to lupus autoantigens and foreign antigens.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- The histone peptide H4 71-94 alone is more effective than a cocktail of peptide epitopes in controlling lupus: immunoregulatory mechanisms.Journal of clinical immunology · 2011Article
- The current concept of T (h) 17 cells and their expanding role in systemic lupus erythematosus.Arthritis · 2011Article
- Epigenetic histone code and autoimmunity.Clinical reviews in allergy & immunology · 2010Review
- The role of B cells in lupus pathogenesis.The international journal of biochemistry & cell biology · 2010Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Nucleosome-specific T helper (Th) cells provide major histocompatibility complex class II-restricted, cognate help to nephritogenic antinuclear autoantibody-producing B cells in lupus. However, the lupus Th cells do not respond when components of the nucleosome, such as free DNA or histones, are individually presented by antigen-presenting cells. Thus critical peptide epitopes for the pathogenic Th cells are probably protected during uptake and processing of the native nucleosome particle as a whole. Therefore, herein we tested 145 overlapping peptides spanning all four core histones in the nucleosome. We localized three regions in core histones, one in H2B at amino acid position 10-33 (H2B(10-33)), and two in H4, at position 16-39 (H4(16-39)) and position 71-94 (H4(71-94)), that contained the peptide epitopes recognized by the pathogenic autoantibody-inducing Th cells of lupus. The peptide autoepitopes also triggered the pathogenic Th cells of (SWR x NZB)F1 lupus mice in vivo to induce the development of severe lupus nephritis. The nucleosomal autoepitopes stimulated the production of Th1-type cytokines, consistent with immunoglobulin IgG2a, IgG2b, and IgG3 being the isotypes of nephritogenic autoantibodies induced in the lupus mice. Interestingly, the Th cell epitopes overlapped with regions in histones that contain B cell epitopes targeted by autoantibodies, as well as the sites where histones contact with DNA in the nucleosome. Identification of the disease-relevant autoepitopes in nucleosomes will help in understanding how the pathogenic Th cells of spontaneous systemic lupus erythematosus emerge, and potentially lead to the development of peptide-based tolerogenic therapy for this major autoimmune disease.
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