Characterization of human memory CD4(+) T-cell responses to the dog allergen Can f 4.
J Allergy Clin Immunol
; 136(4): 1047-54.e10, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-25843313
ABSTRACT
BACKGROUND:
The recently identified dog lipocalin allergen Can f 4 is an important respiratory allergen.OBJECTIVE:
We sought to comprehensively characterize the memory CD4(+) T-cell responses of allergic and nonallergic subjects to Can f 4.METHODS:
Can f 4-specific CD4(+)CD45RO(+) T-cell lines (TCLs) from allergic and healthy subjects were established and characterized by their functional and phenotypic properties. The epitope specificity of the TCLs was tested with 48 overlapping 16-mer peptides spanning the sequence of Can f 4. HLA restriction of the specific TCLs and the binding capacity of the epitope-containing peptides to common HLA class II molecules were studied.RESULTS:
Can f 4-specific memory CD4(+) TCLs were obtained at an 8-fold higher frequency from allergic than from nonallergic subjects. Functionally, the TCLs of allergic subjects exhibited a higher T-cell receptor avidity and expression of CD25 and predominantly produced IL-4 and IL-5. The TCLs of nonallergic subjects mostly secreted IFN-γ and IL-10, with high CXCR3 expression. Several distinct T-cell epitope regions along the allergen were identified. Importantly, the peptides from the region between amino acids 43 and 67 showed promiscuous HLA-binding capacity and induced memory CD4(+) T-cell responses in 90% of the allergic donors.CONCLUSION:
Productive TH2-deviated memory T-cell responses to Can f 4 are observed in allergic but not nonallergic subjects. A 19-mer peptide sequence covering the core of the immunodominant region of the allergen is a potential target for the development of peptide-based allergen immunotherapy.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Alérgenos
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Células Th2
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Lipocalinas
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Hipersensibilidade
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Memória Imunológica
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article