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

Joost W Gouw, Juandy Jo, Laura A P M Meulenbroek, T Sam Heijjer, Erica Kremer, Elena Sandalova, André C Knulst, Prescilla V Jeurink, Johan Garssen, Anneke Rijnierse, Léon M J Knippels

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1345-1353
Number of pages9
JournalClinical and Experimental Allergy
Volume48
Issue number10
DOIs
Publication statusPublished - 5 Jul 2018

Keywords

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

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