Role of conformational and linear epitopes in the achievement of tolerance in cow's milk allergy

Clin Exp Allergy. 2001 Oct;31(10):1599-606. doi: 10.1046/j.1365-2222.2001.01218.x.


Background: Cow's milk (CM) is one of the leading causes of food allergy in children. However, approximately 85% of milk-allergic children become clinically tolerant to CM within the first 3 years of life. The mechanisms involved in the achievement of tolerance remain unknown.

Objective: To study whether IgE antibodies from children with persistent cow's milk allergy (CMA) differ from children who become clinically tolerant in their ability to recognize linear and conformational epitopes of alpha(s1)- and beta-casein.

Methods: Thirty-six milk-allergic children were included in the study: 11 of the children became clinically tolerant, and 25 had persistent CMA. Blood was obtained from all patients during the time they showed clinical reactions to milk challenge. Six non-milk-allergic children served as controls. Specific IgE antibodies against linear (denatured) as well as conformational (native) milk proteins were determined by probing dot-blots with patients' sera. In addition, selected decapeptides from alpha(s1)- and beta-casein, previously found to be suggestive of persistent CMA, were synthesized on a cellulose-derivatized membrane and probed with individual sera from 10 patients who outgrew CMA and from 10 patients with persistent CMA.

Results: Analysis of immunodot-blots showed that, in comparison to tolerant patients, milk-allergic children with persistent symptoms had a significantly higher ratio of specific IgE antibodies to linearized than to native alpha- and beta-casein (P < 0.005 and P < 0.02, respectively). Comparing the selected decapeptides, six of the 10 patients with persistent allergy recognized the peptide corresponding to amino acids 69-78 from alpha(s1)-casein while none of the patients who outgrew CMA had IgE binding to this epitope.

Conclusion: Patients with persistent milk allergy possess higher detectable levels of IgE antibodies to linear epitopes from alpha(s1)- and beta-casein than children who have achieved tolerance. Specific IgE binding to particular linear epitopes in alpha(s1)-casein may be a predictive factor for persistence of CMA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Age Factors
  • Animals
  • Antibody Specificity / immunology
  • Child
  • Child Welfare
  • Child, Preschool
  • Double-Blind Method
  • Epitopes / adverse effects*
  • Epitopes / immunology
  • Epitopes / metabolism*
  • Humans
  • Immune Tolerance / immunology
  • Immune Tolerance / physiology*
  • Immunoblotting
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin E / metabolism
  • Infant
  • Infant Welfare
  • Iodoacetamide / pharmacology
  • Milk Hypersensitivity / etiology*
  • Milk Hypersensitivity / metabolism*
  • Milk Proteins / chemistry
  • Milk Proteins / immunology*
  • Protein Conformation / drug effects
  • Reagent Kits, Diagnostic


  • Epitopes
  • Milk Proteins
  • Reagent Kits, Diagnostic
  • Immunoglobulin E
  • Iodoacetamide