Cited by 448Diabetes and associated disordersT-cell and B-cell Immunologyvaccines and immunoinformatics approaches

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Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes.

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Atkinson, M A, Bowman, M A, Campbell, L, Darrow, B L, Kaufman, D L, Maclaren, N K·1994·Journal of Clinical Investigation

DOI 10.1172/jci117567PMC PMC294659

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Abstract

Insulin-dependent diabetes (IDD) results from the autoimmune destruction of the insulin-producing pancreatic beta cells. Autoreactive T-lymphocytes are thought to play a pivotal role in the pathogenesis of IDD; however, the target antigens of these cells, as well as the inductive events in the disease, are unclear. PBMC in persons with or at increased risk for IDD show elevated reactivity to the beta cell enzyme glutamate decarboxylase (GAD). To identify the T-lymphocyte-reactive determinants of GAD, an overlapping set of synthetic peptides was used to stimulate the PBMC from these individuals, PBMC responsiveness to GAD peptides was not restricted to those with IDD, and a number of peptides elicited responses in PBMC. However, the major determinant of GAD recognized by persons at increased risk for IDD was amino acids 247-279, a region which has significant sequence similarity to the P2-C protein of Coxsackie B virus (47% of 15 increased risk [islet cell autoantibody-positive relatives]; 25% of 16 newly diagnosed IDD patients; and 0% of 13 healthy control subjects). Responses to tetanus and insulin antigens were not different between the study groups. In addition, PBMC from individuals responding to GAD peptides within 247-279 also responded to a Coxsackie viral peptide (i.e., P2-C amino acids 32-47), an observation supporting potential molecular mimicry in this immune response. Although the role of environmental agents in the pathogenesis of the disease remains unclear, these cellular immunological findings support the epidemiological evidence suggesting an inductive role for enteroviruses like Coxsackie B in the autoimmunity underlying IDD.

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Authors: Atkinson, M. A., Bowman, M. A., Campbell, L., Darrow, B. L., Kaufman, D. L., & Maclaren, N. K.
Affiliations: University of Florida (US)
University of Florida Health (US)
University of California, Los Angeles (US)
ORCID: Atkinson, M A
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1994-11-01
Volume: 94
Issue: 5
Pages: 2125-2129
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci117567
PMC: PMC294659
OpenAlex: W2138937703
Cited by: 448
References: 38
Citations by year: 2026: 1 · 2025: 4 · 2024: 9 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 9 · 2015: 9 · 2014: 12 · 2013: 13 · 2012: 11
FWCI: 12.21
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
University of Florida
National Institutes of Health (5r29dk045342-05)
Centers for Disease Control and Prevention
National Institute of Diabetes and Digestive and Kidney Diseases (R29DK45342)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords: type 1 diabetes, glutamic acid decarboxylase, Coxsackie B virus, molecular mimicry, autoreactive T cells, islet autoimmunity, islet autoantibodies, enterovirus, pancreatic beta cells
MeSH terms: Adolescent, Adult, Amino Acid Sequence, Antibodies, Viral, Child, Diabetes Mellitus, Type 1, Enterovirus, Female, Glutamate Decarboxylase, Humans, Immunity, Cellular, Male, Middle Aged, Molecular Sequence Data, Peptide Fragments

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Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes.

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