T cell responses to known allergen proteins are differently polarized and account for a variable fraction of total response to allergen extracts.
A panel of 133 allergens derived from 28 different sources, including fungi, trees, grasses, weeds, and indoor allergens, was surveyed utilizing prediction of HLA class II-binding peptides and ELISPOT assays with PBMC from allergic donors, resulting in the identification of 257 T cell epitopes. More than 90% of the epitopes were novel, and for 14 allergen sources were the first ever identified to our knowledge. The epitopes identified in the different allergen sources summed up to a variable fraction of the total extract response. In cases of allergens in which the identified T cell epitopes accounted for a minor fraction of the extract response, fewer known protein sequences were available, suggesting that for low epitope coverage allergen sources, additional allergen proteins remain to be identified. IL-5 and IFN-γ responses were measured as prototype Th2 and Th1 responses, respectively. Whereas in some cases (e.g., orchard grass, Alternaria, cypress, and Russian thistle) IL-5 production greatly exceeded IFN-γ, in others (e.g., Aspergillus, Penicillum, and alder) the production of IFN-γ exceeded IL-5. Thus, different allergen sources are associated with variable polarization of the responding T cells. The present study represents the most comprehensive survey to date of human allergen-derived T cell epitopes. These epitopes might be used to characterize T cell phenotype/T cell plasticity as a function of seasonality, or as a result of specific immunotherapy treatment or varying disease severity (asthma or rhinitis).
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Carla
C
Oseroff
John
J
Sidney
Randi
R
Vita
Victoria
V
Tripple
Denise M
DM
McKinney
Scott
S
Southwood
Tess M
TM
Brodie
Federica
F
Sallusto
Howard
H
Grey
Rafeul
R
Alam
David
D
Broide
Jason A
JA
Greenbaum
Ravi
R
Kolla
Bjoern
B
Peters
Alessandro
A
Sette
D000485:Allergens / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte