Ranking of immunodominant epitopes in celiac disease: Identification of reliable parameters for the safety assessment of innovative food proteins. (November 2021)

• Record Type: Journal Article
• Authors: Vriz, Riccardo; Moreno, F. Javier; Koning, Frits; Fernandez, Antonio
• Is Part Of: Food and chemical toxicology. Volume 157(2021)
• Publication Date: 2021-11
• Subjects: Celiac disease -- Novel food proteins -- Risk assessment -- Enzymatic digestion -- HLA-DQ -- CD4 T-cells; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2021.112584
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: A ranking of gluten T-cell epitopes triggering celiac disease (CD) for its potential application in the safety assessment of innovative food proteins is developed. This ranking takes into account clinical relevance and information derived from key steps involved in the CD pathogenic pathway: enzymatic digestion, epitope binding to HLA-DQ receptors of the antigen-presenting cells and activation of pro-inflammatory CD4 T-cells, which recognizes the HLA-DQ-epitope complex and initiates the inflammatory response. In silico chymotrypsin digestion was the most discriminatory tool for the ranking of gluten T-cell epitopes among all digestive enzymes studied, classifying 81% and 60% of epitopes binding HLA-DQ2.5 and HLA-DQ8 molecules, respectively, with a high risk. A positive relationship between the number of prolines and the risk of gluten T-cell epitopes was identified. HLA-binding data analysis revealed the additional role played by the flanking regions of the 9-mer epitopes whereas the integration of T-cell activation data into the ranking strategy was incomplete because it was difficult to combine results from different studies. The overall ranking proposed in decreasing order of immunological relevance was: α-gliadins > ω-gliadins > hordeins > γ-gliadins ∼ avenins ∼ secalins > glutenins. This novel approach can be considered as a first step to reshape the risk assessment strategy of innovative proteins and their potential to trigger CD. Highlights: There is a need for a new strategy for the assessment of innovative/novel proteins. A safety ranking of gluten T-cell epitopes triggering celiac disease was developed. In silico chymotrypsin digestion is one of the most discriminatory tools for ranking. The number and position of prolines in the epitopes assessed play a significant role. Ranking by immunological relevance: α-glia > ω-glia > hor > γ-glia ∼ ave ∼ sec > glut.