title: Role of human leucocyte antigen DQ in the presentation of T cell epitopes in the major cow's milk allergen alphas1-casein.
abstract: 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 alphas1-casein, the most abundant milk protein, and to study possible HLA class II allele associations with CMA.
  
  
  METHODS
  alphas1-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 alphas1-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 alphas1-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 alphas1-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.
authors.affiliation: Department of Dermatology/Allergology, University Medical Center, Utrecht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Ruiter
authors.forename: E H
authors.initials: EH
authors.lastname: Rozemuller
authors.forename: A J
authors.initials: AJ
authors.lastname: van Dijk
authors.forename: J
authors.initials: J
authors.lastname: Garssen
authors.forename: C A F M
authors.initials: CA
authors.lastname: Bruijnzeel-Koomen
authors.forename: M G
authors.initials: MG
authors.lastname: Tilanus
authors.forename: E F
authors.initials: EF
authors.lastname: Knol
authors.forename: E
authors.initials: E
authors.lastname: van Hoffen
mesh_terms: D000293:Adolescent; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002364:Caseins / Q000276:immunology*; D002417:Cattle; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007223:Infant; D016269:Milk Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction
chemical_list: D002364:Caseins; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens