Analysis of T cell responses to the major allergens from German cockroach: epitope specificity and relationship to IgE production.
Bla g allergens are major targets of IgE responses associated with cockroach allergies. However, little is known about corresponding T cell responses, despite their potential involvement in immunopathology and the clinical efficacy of specific immunotherapy. Bioinformatic predictions of the capacity of Bla g 1, 2, 4, 5, 6, and 7 peptides to bind HLA-DR, -DP, and -DQ molecules, and PBMC responses from 30 allergic donors, identified 25 T cell epitopes. Five immunodominant epitopes accounted for more than half of the response. Bla g 5, the most dominant allergen, accounted for 65% of the response, and Bla g 6 accounted for 20%. Bla g 5 induced both IL-5 and IFN-γ responses, whereas Bla g 6 induced mostly IL-5, and, conversely, Bla g 2 induced only IFN-γ. Thus, responses to allergens within a source are independently regulated, suggesting a critical role for the allergen itself, and not extraneous stimulation from other allergens or copresented immunomodulators. In comparing Ab with T cell responses for several donor/allergen combinations, we detected IgE titers in the absence of detectable T cell responses, suggesting that unlinked T cell-B cell help might support development of IgE responses. Finally, specific immunotherapy resulted in IL-5 down modulation, which was not associated with development of IFN-γ or IL-10 responses to any of the Bla g-derived peptides. In summary, the characteristics of T cell responses to Bla g allergens appear uncorrelated with IgE responses. Monitoring these responses may therefore yield important information relevant to understanding cockroach allergies and their treatment.
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Carla
C
Oseroff
John
J
Sidney
Victoria
V
Tripple
Howard
H
Grey
Robert
R
Wood
David H
DH
Broide
Jason
J
Greenbaum
Ravi
R
Kolla
Bjoern
B
Peters
Anna
A
Pomés
Alessandro
A
Sette
D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D006682:HLA-DP Antigens / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D019476:Insect Proteins / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014335:Tropomyosin / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; C575000:Bla g 5 allergen, Blattella germanica; C511810:Bla g 6 allergen, Blattella germanica; C481502:Bla g 7 allergen, Blattella germanica; C097505:Blatella germanica allergen 4; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D019476:Insect Proteins; D014335:Tropomyosin; C105482:allergen Bla g 1; D007073:Immunoglobulin E; D016282:Aspartic Acid Endopeptidases; C094699:allergen Bla g 2