title: Differential CD4+ T-cell responses of allergic and non-allergic subjects to the immunodominant epitope region of the horse major allergen Equ c 1.
abstract: The responses of allergen-specific CD4(+) T cells of allergic and healthy individuals are still incompletely understood. Our objective was to investigate the functional and phenotypic properties of CD4(+) T cells of horse-allergic and healthy subjects specific to the immunodominant epitope region of the major horse allergen Equ c 1. Specific T-cell lines (TCLs) and clones were generated from peripheral blood mononuclear cells with Equ c 1(143-160), the peptide containing the immunodominant epitope region of Equ c 1. The frequency, proliferative response, cytokine production and HLA restriction of the cells were examined. The frequency of Equ c 1-specific CD4(+) T cells was low (approximately 1 per 10(6) CD4(+) T cells) in both allergic and non-allergic subjects. The cells of allergic subjects had a stronger proliferative capacity than those of non-allergic subjects, and they predominantly emerged from the memory T-cell pool and expressed the T helper type 2 cytokine profile, whereas the cells of non-allergic subjects emerged from the naive T-cell pool and produced low levels of interferon-γ and interleukin-10. T-cell response to Equ c 1(143-160) was restricted by several common HLA class II molecules from both DQ and DR loci. As the phenotypic and functional properties of Equ c 1-specific CD4(+) T cells differ between allergic and non-allergic subjects, allergen-specific T cells appear to be tightly implicated in the development of diseased or healthy outcome. Restriction of the specific CD4(+) T-cell response by multiple HLA alleles suggests that Equ c 1(143-160) is a promising candidate for peptide-based immunotherapy.
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocentre Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Anssi
authors.initials: A
authors.lastname: Kailaanmäki
authors.forename: Tuure
authors.initials: T
authors.lastname: Kinnunen
authors.forename: William W
authors.initials: WW
authors.lastname: Kwok
authors.forename: Marja
authors.initials: M
authors.lastname: Rytkönen-Nissinen
authors.forename: Jukka
authors.initials: J
authors.lastname: Randell
authors.forename: Tuomas
authors.initials: T
authors.lastname: Virtanen
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006736:Horses; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D054834:Lipocalins; D008297:Male; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000485:Allergens; D018984:Epitopes, T-Lymphocyte; C103025:Equ c1 allergen, Equus caballus; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; C573415:IFNG protein, human; C508609:IL10 protein, human; D054834:Lipocalins; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: CD4+ T-cell response; Equ c 1; frequency; horse; lipocalin allergen