ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Structure-based selection of small molecules to alter allele-specific MHC class II antigen presentation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
47 citing papers in PubMed, 63 citations in OpenAlex.
- From Disposal to Display: Crinophagy as a β-Cell Source of Neoantigens in Type 1 Diabetes.Immunological reviews · 2026Review
- Exploring MHC class II I-Ab blockade as a potential treatment for Sjögren's disease in the mouse model.ImmunoHorizons · 2025Article
- Self-Antigens Targeted by Regulatory T Cells in Type 1 Diabetes.International journal of molecular sciences · 2022Review
- Blocking IAgLife sciences · 2022Article
- Diabetes type 1: Can it be treated as an autoimmune disorder?Reviews in endocrine & metabolic disorders · 2021Review
- Noncontiguous T cell epitopes in autoimmune diabetes: From mice to men and back again.The Journal of biological chemistry · 2021Review
- Cepharanthine blocks TSH receptor peptide presentation by HLA-DR3: Therapeutic implications to Graves' disease.Journal of autoimmunity · 2020Article
- Evolutionary Pattern of Interferon Alpha Genes in Bovidae and Genetic Diversity of IFNAA in the Bovine Genome.Frontiers in immunology · 2020Article
- Negative selection of human T cells recognizing a naturally-expressed tissue-restricted antigen in the human thymus.Journal of translational autoimmunity · 2020Article
- Identification of drug-specific public TCR driving severe cutaneous adverse reactions.Nature communications · 2019Article
- The Immunoreactive Platform of the Pancreatic Islets Influences the Development of Autoreactivity.Diabetes · 2019Article
- Rationally designed small molecules to prevent type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2019Review
- Structure-based selection of human metabolite binding P4 pocket of DRB1*15:01 and DRB1*15:03, with implications for multiple sclerosis.Genes and immunity · 2019Article
- Determining Antigen Specificity of Human Islet Infiltrating T Cells in Type 1 Diabetes.Frontiers in immunology · 2019Review
- Learning From Past Failures of Oral Insulin Trials.Diabetes · 2018Article
- Methyldopa blocks MHC class II binding to disease-specific antigens in autoimmune diabetes.The Journal of clinical investigation · 2018Article
- Type 1 Diabetes TrialNet: A Multifaceted Approach to Bringing Disease-Modifying Therapy to Clinical Use in Type 1 Diabetes.Diabetes care · 2018Article
- Type 1 diabetes induction in humanized mice.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Ectopic Expression of Self-Antigen Drives Regulatory T Cell Development and Not Deletion of Autoimmune T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules.Journal of visualized experiments : JoVE · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Class II major histocompatibility molecules are the primary susceptibility locus for many autoimmune disorders, including type 1 diabetes. Human DQ8 and I-A(g7), in the NOD mouse model of spontaneous autoimmune diabetes, confers diabetes risk by modulating presentation of specific islet peptides in the thymus and periphery. We used an in silico molecular docking program to screen a large "druglike" chemical library to define small molecules capable of occupying specific structural pockets along the I-A(g7) binding groove, with the objective of influencing presentation to T cells of the autoantigen insulin B chain peptide consisting of amino acids 9-23. In this study we show, using both murine and human cells, that small molecules can enhance or inhibit specific TCR signaling in the presence of cognate target peptides, based upon the structural pocket targeted. The influence of compounds on the TCR response was pocket dependent, with pocket 1 and 6 compounds inhibiting responses and molecules directed at pocket 9 enhancing responses to peptide. At nanomolar concentrations, the inhibitory molecules block the insulin B chain peptide consisting of amino acids 9-23, endogenous insulin, and islet-stimulated T cell responses. Glyphosine, a pocket 9 compound, enhances insulin peptide presentation to T cells at concentrations as low as 10 nM, upregulates IL-10 secretion, and prevents diabetes in NOD mice. These studies present a novel method for identifying small molecules capable of both stimulating and inhibiting T cell responses, with potentially therapeutic applications.
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Registered trials
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