T cell epitopes of house dust mite major allergen Der p II.
Recent work has indicated the significance of IL-4- and IL-5-secreting allergen-specific human Th2 lymphocytes in the control of immune responses to allergens in atopic individuals. The precise allergenic epitopes that activate these allergen-specific Th2 cells are, however, hardly known. We analyzed the epitope-specificity of T lymphocytes specific for Der p II, one of the major allergens of house dust mite Dermatophagoides pteronyssinus. Using a panel of overlapping synthetic peptides that span the entire Der p II molecule, we could demonstrate that polyclonal Der p II-specific T cell lines prepared from the peripheral blood of five atopic patients can react with at least 10 different epitopes of the molecule. Each donor showed a different pattern of reactivity with the synthetic peptides, suggesting that Der p II contains multiple T cell epitopes that may differ from individual to individual. We studied the specificity of the T cell response to Der p II in more detail in one atopic patient using a short term polyclonal T cell line that strongly reacted to one single peptide (116-129) of the allergen. From this patient we established a panel of 11 Der p II-specific TLC. Ten TLC were of the CD3+ CD4+ phenotype and showed a high IL-4/IFN-gamma production ratio, whereas another TLC expressed CD3 and CD8 and failed to secrete substantial IL-4 and IFN-gamma. The use of at least four different TCR V beta gene segments was shown within this panel TLC. All TLC tested recognized the allergen in an HLA-DR1-restricted manner. Although this patient reacted to only one peptide on the polyclonal level, two T cell epitopes were identified on the clonal level by using synthetic peptides and autologous APC to stimulate the TLC. Combining data of CD4/CD8 expression, TCR V beta usage, and epitope specificity, at least six different types of Der p II-specific TLC could be identified within this patient. Binding of IgE to all synthetic peptides of Der p II is low and of low affinity, which may be of particular importance with respect to possible desensitization protocols using such peptides.
Joost van Neerven
R
R
Laboratory for Cell Biology and Histology, University of Amsterdam, Academisch Medisch Centrum, The Netherlands.
van t'Hof
W
W
Ringrose
J H
JH
Jansen
H M
HM
Aalberse
R C
RC
Wierenga
E A
EA
Kapsenberg
M L
ML
D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides; D002478:Cells, Cultured; D000939:Epitopes; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006023:Glycoproteins / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008925:Mites / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D039741:Antigens, Dermatophagoides; D000939:Epitopes; D006023:Glycoproteins; D006684:HLA-DR Antigens; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007073:Immunoglobulin E