Clonal analysis of the atopic immune response to the group 2 allergen of Dermatophagoides spp.: identification of HLA-DR and -DQ restricted T cell epitopes.
The group 2 allergens of Dermatophagoides spp. (house dust mite, HDM) are a major immunological target for IgE antibodies in the allergic immune response of HDM atopic individuals. In this report the heterogeneity of the T cell repertoire reactive with the group 2 allergen of Dermatophagoides pteronyssinus (Der p 2) of a HDM allergic individual was investigated using overlapping synthetic peptides. By clonal analysis four distinct T cell epitopes were identified, located within residues 16-31, 22-40, 82-100, and 111-129. The importance of these epitopes was confirmed by investigation of the peripheral T cell repertoire, with the polyclonal T cell response to Der p 2 failing to show marked variations in epitope specificity over time. Serological inhibition studies and the use of Epstein-Barr virus transformed B cell lines characterized for their expression of HLA-D region gene products demonstrated that recognition of peptides 16-31 and 111-129 was restricted by HLA-DQ (DQB1*0301), whereas peptide 82-100 is recognized in association with HLA-DR (DRB1*1101). Peptide 22-40 was presented by both HLA-DRB1*1101 and -DQB1*0301 class II molecules. The potential application of these findings lies in the design of peptide-based immunotherapeutics for the management of HDM allergic disease.
Verhoef
A
A
Department of Immunology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
Higgins
J A
JA
Thorpe
C J
CJ
Marsh
S G
SG
Hayball
J D
JD
Lamb
J R
JR
O'Hehir
R E
RE
D000595:Amino Acid Sequence; D000818:Animals; D039741:Antigens, Dermatophagoides; D002999:Clone Cells; D000939:Epitopes / Q000032:analysis*; D006023:Glycoproteins / Q000276:immunology; D006683:HLA-DQ Antigens / Q000502:physiology*; D006684:HLA-DR Antigens / Q000502:physiology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D008925:Mites / Q000276:immunology*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D000939:Epitopes; D006023:Glycoproteins; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens