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Clin Exp Allergy. 2018 Oct;48(10):1345-1353. doi: 10.1111/cea.13223. Epub 2018 Aug 14.

Identification of peptides with tolerogenic potential in a hydrolysed whey-based infant formula.

Author information

1
Danone Nutricia Research, Utrecht, The Netherlands.
2
Danone Nutricia Research, Singapore.
3
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
4
Department of Dermatology and Allergology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

Abstract

BACKGROUND:

Failure to induce oral tolerance may result in food allergy. Hydrolysed cow's milk-based infant formulas are recommended in subjects with a high risk of developing allergic disease. Presentation of T cell epitopes is a prerequisite to generate regulatory T cells that could contribute to oral tolerance.

OBJECTIVE:

To investigate whether a specific hydrolysed whey-based infant formula contains peptides that function as T cell epitopes to support the development of oral tolerance to whey.

METHODS:

First, a novel liquid chromatography-mass spectrometry (LC-MS) method was developed to characterize β-lactoglobulin-derived peptides present in a specific infant formula with a focus on region AA#13-48 of β-lactoglobulin, which has previously been described to contain T cell epitopes with tolerogenic potential. Second, the formula was subjected to the ProImmune ProPresent® antigen presentation assay and MHC class II binding algorithm to identify relevant HLA-DRB1-restricted peptides. Third, identified peptides were tested on human cow's milk protein-specific T cell lines to determine T cell recognition.

RESULTS:

Thirteen peptides of minimal 9AAs long that overlap with AA#13-48 of β-lactoglobulin were identified. Six of them were found across all batches analysed. It was further confirmed that these peptides were processed and presented by human dendritic cells. The identified HLA-DRB1-restricted peptides were correlated to AA#11-30 and AA#23-39 of β-lactoglobulin. Importantly, the proliferation assay showed that the synthetic peptides were recognized by cow's milk protein-specific T cell lines and induced T cell proliferation.

CONCLUSION AND CLINICAL RELEVANCE:

This study demonstrates that the tested hydrolysed infant formula contains functional HLA-DRB1-restricted T cell epitopes, which can potentially support the development of oral tolerance to whey.

KEYWORDS:

T cell epitope; food allergy; infant formula; oral tolerance; peptidomics

PMID:
29974988
DOI:
10.1111/cea.13223

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