ArticleProceedings of the National Academy of Sciences of the United States of America2015
N-terminal additions to the WE14 peptide of chromogranin A create strong autoantigen agonists in type 1 diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Mechanisms of B Cell Tolerance in Health and Autoimmunity.Arthritis & rheumatology (Hoboken, N.J.) · 2026Review
- The role of chromogranin A cleavage products in onset of type 1 and 2 diabetes.Frontiers in clinical diabetes and healthcare · 2026Review
- Essential role of interferon-regulatory factor 4 in regulating diabetogenic CD4+ T and innate immune cells in autoimmune diabetes in NOD mice.Clinical and experimental immunology · 2025Article
- A complex role of chromogranin A and its peptides in inflammation, autoimmunity, and infections.Frontiers in immunology · 2025Review
- Immunotherapy for Type 1 Diabetes: Mechanistic Insights and Impact of Delivery Systems.Current pharmaceutical design · 2025Review
- Non-mutational neoantigens in disease.Nature immunology · 2024Review
- Antigen-specific T cell responses in autoimmune diabetes.Frontiers in immunology · 2024Review
- Soluble antigen arrays provide increased efficacy and safety over free peptides for tolerogenic immunotherapy.Frontiers in immunology · 2024Article
- Epitope-based precision immunotherapy of Type 1 diabetes.Human vaccines & immunotherapeutics · 2023Article
- Selected Serum Markers Associated with Pathogenesis and Clinical Course of Type 1 Diabetes in Pediatric Patients-The Effect of Disease Duration.Journal of clinical medicine · 2023Article
- Using mass spectrometry to identify neoantigens in autoimmune diseases: The type 1 diabetes example.Seminars in immunology · 2023Review
- Calcitonin gene-related peptide is a potential autoantigen for CD4 T cells in type 1 diabetes.Frontiers in immunology · 2022Article
- A Novel Tolerogenic Antibody Targeting Disulfide-Modified Autoantigen Effectively Prevents Type 1 Diabetes in NOD Mice.Frontiers in immunology · 2022Article
- Know thy immune self and non-self: Proteomics informs on the expanse of self and non-self, and how and where they arise.Proteomics · 2021Review
- Role and function of granin proteins in diabetes mellitus.World journal of diabetes · 2021Review
- Lysosomal cathepsin creates chimeric epitopes for diabetogenic CD4 T cells via transpeptidation.The Journal of experimental medicine · 2021Article
- Hidden in Plain View: Discovery of Chimeric Diabetogenic CD4 T Cell Neo-Epitopes.Frontiers in immunology · 2021Review
- A biomimetic five-module chimeric antigen receptor (Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Challenges of Identifying Environmental Determinants of Type 1 Diabetes: In Search of the Holy Grail.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Review
- Chromogranin A and its fragments in cardiovascular, immunometabolic, and cancer regulation.Annals of the New York Academy of Sciences · 2019Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Chromogranin A (ChgA) is an autoantigen for CD4(+) T cells in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D). The natural ChgA-processed peptide, WE14, is a weak agonist for the prototypical T cell, BDC-2.5, and other ChgA-specific T-cell clones. Mimotope peptides with much higher activity share a C-terminal motif, WXRM(D/E), that is predicted to lie in the p5 to p9 position in the mouse MHC class II, IA(g7) binding groove. This motif is also present in WE14 (WSRMD), but at its N terminus. Therefore, to place the WE14 motif into the same position as seen in the mimotopes, we added the amino acids RLGL to its N terminus. Like the other mimotopes, RLGL-WE14, is much more potent than WE14 in T-cell stimulation and activates a diverse population of CD4(+) T cells, which also respond to WE14 as well as islets from WT, but not ChgA(-/-) mice. The crystal structure of the IA(g7)-RLGL-WE14 complex confirmed the predicted placement of the peptide within the IA(g7) groove. Fluorescent IA(g7)-RLGL-WE14 tetramers bind to ChgA-specific T-cell clones and easily detect ChgA-specific T cells in the pancreas and pancreatic lymph nodes of NOD mice. The prediction that many different N-terminal amino acid extensions to the WXRM(D/E) motif are sufficient to greatly improve T-cell stimulation leads us to propose that such a posttranslational modification may occur uniquely in the pancreas or pancreatic lymph nodes, perhaps via the mechanism of transpeptidation. This modification could account for the escape of these T cells from thymic negative selection.
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