Premium
Characterization of T cell epitopes in αs1‐casein in cow's milk allergic, atopic and non‐atopic children
Author(s) -
Ruiter B.,
Trégoat V.,
M'Rabet L.,
Garssen J.,
BruijnzeelKoomen C. A. F. M.,
Knol E. F.,
Hoffen E.
Publication year - 2006
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2006.02436.x
Subject(s) - epitope , milk allergy , casein , immunology , t cell , peripheral blood mononuclear cell , allergen , immunoglobulin e , allergy , cytokine , biology , antibody , immune system , biochemistry , in vitro
Summary Background One to two percent of infants suffer from IgE‐mediated allergic reactions against cow's milk proteins. Most children develop clinical tolerance, but approximately 15% are still allergic by the age of 10 years. Little is known about the T cell epitopes in individual cow's milk protein in relation to allergy and tolerance. Objective To identify T cell epitopes in αs1‐casein, the most abundant milk protein, and to investigate T cell responses toward these epitopes in allergic, atopic and non‐atopic children. Methods Allergen‐specific T cell lines (TCLs) were derived from peripheral blood mononuclear cells of 11 cow's milk allergic, nine atopic and nine non‐atopic children. T cell responses were measured to αs1‐casein and to overlapping peptides (18‐mers), spanning the αs1‐casein molecule. Proliferation was determined by incorporation of 3 H‐thymidine, and cytokine production (IL‐10, IL‐13 and IFN‐γ) was measured by ELISA. Results Four main regions (amino acid (AA) residues 43–66, 73–96, 91–114 and 127–180) in the αs1‐casein molecule were immunogenic to T cells, among which the AA residues 133–156 spanned the immunodominant part. Only subtle differences were found in peptide recognition between the subject groups. Some of the peptides induced slightly Th1‐ or Th2‐skewed cytokine responses. The increased levels of IL‐10 in response to αs1‐casein observed in TCLs from atopic children appeared not to be linked to recognition of specific IL‐10‐inducing epitopes. Conclusions The immunodominant sequence in αs1‐casein is spanned by AA residues 133–156. Tolerance towards αs1‐casein in atopic children may be mediated by an overall induction of IL‐10 and not by recognition of certain T cell epitopes. The identified T cell epitopes in children with cow's milk allergy may be useful targets in developing peptide immunotherapy.