T Cell Epitope-Containing Peptides of the Major Dog Allergen Can f 1 as Candidates for Allergen Immunotherapy

Abstract

One prerequisite for developing peptide-based allergen immunotherapy is knowing the T cell epitopes of an allergen. In this study, human T cell reactivity against the major dog allergen Can f 1 was investigated to determine peptides suitable for immunotherapy. Seven T cell epitope regions (A–G) were found in Can f 1 with specific T cell lines and clones. The localization of the epitope regions shows similarities with those of the epitopes found in Bos d 2 and Rat n 1. On average, individuals recognized three epitopes in Can f 1. Our results suggest that seven 16-mer peptides (p15–30, p33–48, p49–64, p73–88, p107–122, p123–138, and p141–156), each from one of the epitope regions, show widespread T cell reactivity in the population studied, and they bind efficiently to seven HLA-DRB1 molecules (DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, DRB1*1101, DRB1*1301, and DRB1*1501) predominant in Caucasian populations. Therefore, these peptides are potential candidates for immunotherapy of dog allergy.

T-cell responses to allergens

“…63,[78][79][80][81][82][83][84][85][86] Although some allergens (eg, Fel d 1) contain broad immunodominant regions encompassing multiple nested epitopes, other allergens (eg, Can f 1) contain many epitopes scattered throughout the molecule. 63,84,87 On the other hand, for some inhalant allergens (eg, mugwort), T-cell responses may be dominated by a single epitope. 88,89 In those cases, mapping of epitopes to conserved regions of the molecule that cross-react with related food allergens may preferentially drive T-cell recognition of these epitopes.…”

Not all proteins are created allergens

“…Specifically, the implication was that high-dose exposure to cat allergen generates an increased density of T-cell epitopes on the antigen-presenting cell compared with mite allergen and that this favors skewing of the response to cat allergen away from a T H 2 response toward the development of tolerance. 3,4 As Drs Virtanen and Kinnunen point out, the allergenicity of distinct proteins is unlikely to be simply explained by differences in biologic function. Their suggestion that Der p 1 invokes T H 2 responses through presentation of antigenic peptide at low concentrations is consistent with the author's view.…”

“…We have found that the reactivity of PBMCs to several lipocalin allergens (ie, cow Bos d 2, dog Can f 1, and horse Equ c 1) is weak. 4,5 Most probably, one of the reasons is that specific T cells are present in low numbers in the periphery. 5 Moreover, induction of lipocalin allergen-specific T-cell lines has proved to be laborious, and the proliferative capacity of the lines on stimulation with the allergens is only moderate.…”

“…Considering the important group of respiratory animal allergens, lipocalins, their weak TCR recognition is conceivable because these proteins can exhibit considerable amino acid identity between species, up to about 60%, which is the case between dog Can f 1 and human tear lipocalin. 4 Therefore T H cells with strong reactivity to lipocalin proteins and allergens can be absent in human subjects because of thymic deletion. Our findings are in accordance with this hypothesis.…”

Characterization of Dog Allergens Can f 1 and Can f 2. 1. Preparation of Their Recombinant Proteins and Antibodies

“…In houses, the dog allergens become airborne as smaller-sized particles [11, 19], but we do not know why the dog allergens become such small particles. Recently, the T cell epitopes of Can f 1 and of Can f 2 were analyzed using the overlapped peptides in T cell proliferation assays [20]. In that study, certain kinds of the peptides were found to be candidates; however, IgE binding and IgE production were not examined.…”