title: Characterization of human memory CD4(+) T-cell responses to the dog allergen Can f 4.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland. Electronic address: aino.liukko@uef.fi.
authors.forename: Aino L
authors.initials: AL
authors.lastname: Rönkä
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tuure T
authors.initials: TT
authors.lastname: Kinnunen
authors.affiliation: Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies, Service d'Ingénierie Moléculaire des Protéines, Gif-Sur-Yvette, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Goudet
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland; Institute of Dentistry, School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marja A
authors.initials: MA
authors.lastname: Rytkönen-Nissinen
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Joni
authors.initials: J
authors.lastname: Sairanen
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Anssi H T
authors.initials: AH
authors.lastname: Kailaanmäki
authors.affiliation: Department of Pulmonary Diseases, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Jukka T
authors.initials: JT
authors.lastname: Randell
authors.affiliation: Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies, Service d'Ingénierie Moléculaire des Protéines, Gif-Sur-Yvette, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillère
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tuomas I
authors.initials: TI
authors.lastname: Virtanen
mesh_terms: D000485:Allergens / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007156:Immunologic Memory; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D054834:Lipocalins / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D054367:Receptors, CXCR3 / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; C515187:CXCR3 protein, human; C000590661:Can f 4 allergen, Canis familiaris; D016207:Cytokines; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D054834:Lipocalins; D054367:Receptors, CXCR3
keywords: Can f 4; HLA class II; Memory T cells; T(H)1/T(H)2; T-cell epitope; allergy; immunotherapy; lipocalin allergen; peptide