Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein

• Published in: International archives of allergy and immunology Vol. 143; no. 2; pp. 119 - 126
• Main Authors: Ruiter, B., Rozemuller, E.H., van Dijk, A.J., Garssen, J., Bruijnzeel-Koomen, C.A.F.M., Tilanus, M.G., Knol, E.F., van Hoffen, E.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2007
• Subjects: Allergic diseases; Biological and medical sciences; Digestive allergic diseases; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunopathology; Medical sciences; Original Paper; αs1-Casein; T cell epitope; Human leucocyte antigen DQ; Cow's milk allergy; Immunopathology; Food allergy; HLA-System; Antigenic determinant; Immunology; Casein; T-Lymphocyte; Digestive diseases; Cow milk; Allergen
• DOI: 10.1159/000098660
• ISSN: 1018-2438

Background: Little is known about the association between human leucocyte antigen (HLA) and cow’s milk allergy (CMA). The aim of the present study was to determine the HLA restriction of T cell clones (TCCs) specific to αs1-casein, the most abundant milk protein, and to study possible HLA class II allele associations with CMA. Methods: αs1-Casein-specific TCCs were derived from 6 children with CMA, 9 atopic children without CMA and 5 non-atopic children. T cell epitope specificity was defined by stimulation with overlapping peptides, spanning the αs1-casein molecule. HLA restriction was determined in proliferation assays using antibodies blocking either HLA-DP, HLA-DQ or HLA-DR. HLA genotyping was performed in 32 subjects with CMA, 23 atopic and 22 non-atopic individuals. Results: Ten TCCs were restricted to HLA-DQ, 6 TCCs to HLA-DR and 4 TCCs to HLA-DP. The sequence in αs1-casein that was most immunogenic to T cells from children with CMA contained T cell epitopes restricted to DQB1*0201, DPB1*0401 and DRB1*1501. The DQB1*0501 allele frequency was lower in children with CMA than in non-atopic children, but this difference could not be confirmed in an additional group of subjects with and without CMA. Conclusions: HLA-DQ plays a substantial role in the presentation of T cell epitopes in αs1-casein. However, HLA class II allele frequencies do not show major differences between cow’s milk allergic, atopic and non-atopic subjects. T cell epitopes in the most immunogenic region are presented by various abundantly present HLA genotypes. Therefore, this sequence may be a suitable target for peptide immunotherapy.