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How Are Food Protein-Derived Antigens Involved In Type-1 Diabetes? [Jun Wei]
1. Creating the University of the Highlands and Islands
Department of Diabetes
and Cardiovascular
Science
How are the food protein-How are the food protein-
derived antigens involvedderived antigens involved
in type-1 diabetes?in type-1 diabetes?
Jun Wei, MD, PhD
2. Type-1 Diabetes (T1D)
• Autoimmune disorder
Immune-mediated beta-cell
destruction
• Age of onset
Childhood
• Prevalence
0.4% affected in the European
population
10. Features of Dietary Gliadins
• Rich in proline and glutamine
Xaa-Pro-Gln sites
• Resistant to digestive enzymes
Trypsin, pepsin and chymotrypsin
• Antigens
CD4+ T-cell restricted
11. Cow Milk Caseins
• Milk proteins
Casein & whey proteins
Isoforms: α-s1, α-s2, ß & κ
• Polymorphisms
13 forms of ß-casein
Frequency varies in cows
12. Bioactive Peptides inβ-Casein
• Rich in proline
Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn-
Ser-Leu
• β-casomorphins
Tyr-Pro-Phe-Gly-Pro-Ile-Pro (BCM7)
related to many conditions
13. Permeability of the Gut in T1D
Gluten peptides
Increased
permeability
Deamidated
by TGM2APC
CD4+T
cell
Villous epithelia
14. Gluten Hypothesis for T1D
Permeability altered
Influx of gluten
Modified by TGM2
Binding to DQ8 molecules
T cell response toward Ab
T1D
17. Research Strategies
• Correlations between auto-Abs and
Abs to gluten and caseins
• Identification of toxic fragments
• Identification of low toxic strain of
wheat
18. Acknowledgements
• Scottish Funding Council
• Highlands & Islands Enterprise
• European Regional Development
Fund
• Schizophrenia Association of Great
Britain
• NHS Highland R&D Office