ArticleProceedings of the National Academy of Sciences of the United States of America2006
DRB1*0401-restricted human T cell clone specific for the major proinsulin73-90 epitope expresses a down-regulatory T helper 2 phenotype.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 44 citations in OpenAlex.
- Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes.Genome medicine · 2024Article
- Insulin B-chain hybrid peptides are agonists for T cells reactive to insulin B:9-23 in autoimmune diabetes.Frontiers in immunology · 2022Article
- Characterization of Proinsulin T Cell Epitopes Restricted by Type 1 Diabetes-Associated HLA Class II Molecules.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Monitoring T-Cell Responses in Translational Studies: Optimization of Dye-Based Proliferation Assay for Evaluation of Antigen-Specific Responses.Frontiers in immunology · 2017Article
- Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice.Nature communications · 2016Article
- Article
- In vitro and in vivo studies of IgG-derived Treg epitopes (Tregitopes): a promising new tool for tolerance induction and treatment of autoimmunity.Journal of clinical immunology · 2013Review
- Application of IgG-derived natural Treg epitopes (IgG Tregitopes) to antigen-specific tolerance induction in a murine model of type 1 diabetes.Journal of diabetes research · 2013Article
- ZnT8-Specific CD4+ T cells display distinct cytokine expression profiles between type 1 diabetes patients and healthy adults.PloS one · 2013Article
- Teaching tolerance: New approaches to enzyme replacement therapy for Pompe disease.Human vaccines & immunotherapeutics · 2012Article
- Islet autoantigens: structure, function, localization, and regulation.Cold Spring Harbor perspectives in medicine · 2012Review
- T cell recognition of autoantigens in human type 1 diabetes: clinical perspectives.Clinical & developmental immunology · 2011Review
- Current approaches to measuring human islet-antigen specific T cell function in type 1 diabetes.Clinical and experimental immunology · 2010Review
- Peptide-MHC cellular microarray with innovative data analysis system for simultaneously detecting multiple CD4 T-cell responses.PloS one · 2010Article
- Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin.Genes and immunity · 2010Article
- The A-chain of insulin is a hot-spot for CD4+ T cell epitopes in human type 1 diabetes.Clinical and experimental immunology · 2009Article
- Article
- High-content T-cell and B-cell analysis.Clinical reviews in allergy & immunology · 2007Article
- Replenishing Peripheral CD4(+) Regulatory T Cells: A Possible Immune-Intervention Strategy in Type 1 Diabetes?The review of diabetic studies : RDS · 2006Article
Corrections and comments
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Authors and funding
21 authors at 10 institutions in 5 countries.
Funding
Abstract
Recently, we have identified proinsulin (P-Ins)(73-90) as an immunodominant T cell epitope of HLA-DRB1*0401 (DR4) subjects with beta-islet cell autoimmunity and of HLA-DR4/CD4 double-transgenic mice immunized with human P-Ins. We have compared the fine specificities of one human CD4 T cell clone and two mouse T cell hybridoma clones recognizing this epitope, and, although these three clones all recognized the same core region (LALEGSLQK), there were major differences in how they interacted with the peptide (p)/HLA complex, reflecting the fact that human P-Ins is a foreign antigen in the mouse and an autoantigen in the type 1 diabetes patient. The human T cell clone was forkhead transcription factor 3 (Foxp3)-positive, a marker for regulatory T cell lineages, and secreted predominantly IL-5, IL-10, and low levels of IFNgamma in response to P-Ins(73-90). This finding is compatible with the previously detected regulatory cytokine pattern in subjects with beta-cell autoimmunity. However, added N- or C-terminal amino acids drastically changed HLA and tetramer binding capacity as well as T cell reactivity and the cytokine phenotype of the P-Ins(73-90)-specific human CD4 T cell clone, suggesting a potential for this P-Ins epitope as a target for therapeutic intervention in HLA-DR4-positive humans with beta-islet cell autoimmunity or recent-onset type 1 diabetes.
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