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 3H-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.