Highly heterogeneous Phl p 5-specific T cells from patients with allergic rhinitis differentially recognize recombinant Phl p 5 isoallergens.
BACKGROUND
The prevalence of atopic allergy to Poaceae grasses poses a serious health problem.


OBJECTIVE
To evaluate the T cell-activating capacity of recombinant grass pollen allergens suggested for immunotherapy, we characterized the T-cell response of allergic patients to the Phleum pratense (Phl p) major allergen, Phl p 5.


METHODS
Thirty-eight Phl p 5-specific CD4(+) T-cell clones (TCCs) were isolated from the peripheral blood of 3 patients with allergic rhinitis and were characterized with respect to cross-reactivity, HLA restriction, cytokine profiles, and isoallergen specificity when tested with natural Phl p 5 and 5 rPhl p 5 isoallergens (4 Phl p 5a and 1 Phl p 5b).


RESULTS
The TCCs were highly cross-reactive with group 5 allergens of related grasses, and the different cross-reactivity patterns found indicate that several T-cell epitopes are present in Phl p 5. Most TCCs displayed a TH0-like cytokine profile, whereas a few TCCs belonged to the TH2 or TH1 subset. The TCCs were restricted by HLA-DR (24/38 TCCs), HLA-DQ (11/38 TCCs), or HLA-DP (3/38 TCCs). Interestingly, 4 of the 34 TCCs tested reacted exclusively with the 4 rPhl p 5a isoforms; 8 of 34 TCCs were rPhl p 5b specific, and 3 of 34 TCCs reacted with all isoforms; 19 of 34 TCCs did not react with any of the rPhl p 5 isoallergens. Moreover, the overall isoform recognition pattern differed considerably among patients.


CONCLUSIONS
These results demonstrate that Phl p 5-specific T cells are highly heterogeneous and that individual TCCs, and individual patients, differentially recognize isoallergens. The differential isoallergen recognition for Phl p 5-specific T cells suggests, if confirmed in larger patient groups, that a combination of 2 or more rPhl p 5 isoallergens may be needed to replace the natural grass allergen for immunotherapy.
Würtzen
P
P
ALK Abelló, Horsholm; Laborgruppe Allergologie, Forschungszentrum Borstel, Germany.
Wissenbach
M
M
Ipsen
H
H
Bufe
A
A
Arnved
J
J
van Neerven
R J
RJ
D000485:Allergens / Q000032:analysis; D000595:Amino Acid Sequence; D001782:Blood Donors; D002999:Clone Cells / Q000166:cytology; D003429:Cross Reactions; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000032:analysis / Q000276:immunology*; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000032:analysis*; D020033:Protein Isoforms / Q000737:chemistry; D011994:Recombinant Proteins / Q000032:analysis / Q000737:chemistry; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000276:immunology*; D012260:Ribonucleases / Q000032:analysis*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000485:Allergens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D010940:Plant Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; C102306:Phl p Vb protein, Phleum pratense; D012260:Ribonucleases