title: Human memory CD4+ T cell response to the major dog allergen Can f 5, prostatic kallikrein.
abstract: Human CD4+ T cell responses to important animal allergens are still insufficiently understood.
  
  
  
  To comprehensively characterize in vitro and ex vivo the peripheral blood memory CD4+ T cell responses of subjects with and without allergy to the major dog allergen Can f 5, the only known animal allergen in the kallikrein family of proteins.
  
  
  
  Can f 5-specific memory CD4+ T cell lines (TCLs) were established from the peripheral blood of 12 subjects with and 12 subjects without allergy to Can f 5 and characterized for their functional and phenotypic properties. The results were evaluated with those obtained ex vivo with a novel CD154 enrichment method. The epitopes recognized by the Can f 5-specific TCLs were determined with 72 overlapping 16-mer peptides covering the sequence of the allergen.
  
  
  
  Can f 5-specific TCLs were obtained at about tenfold higher frequency from allergic than from non-allergic subjects. Functionally, the TCLs of allergic subjects displayed a Th2-biased cytokine phenotype and increased T cell receptor avidity, whereas the TCLs of non-allergic subjects displayed a Th1-/Th0-biased cytokine phenotype and lower TCR avidity. The higher frequency and the Th2 phenotype of Can f 5-specific memory CD4+ T cells in allergic subjects were confirmed by the CD154 enrichment method ex vivo. Six distinct T cell epitope regions of Can f 5 were predominantly recognized by the TCLs from allergic subjects.
  
  
  
  Can f 5-specific memory CD4+ T cell responses differ considerably between subjects with and without allergy, as assessed by both in vitro and ex vivo approaches. Peptides containing the dominant T cell epitopes of Can f 5 can be employed for developing peptide-based immunotherapy for dog allergy.
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Kailaanmäki
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Kinnunen
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Rönkä
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: M
authors.identifier: 0000-0002-2014-8315
authors.initials: M
authors.lastname: Rytkönen-Nissinen
authors.affiliation: Thermo Fisher Scientific, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Lidholm
authors.affiliation: Thermo Fisher Scientific, Uppsala, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Mattsson
authors.affiliation: Department of Pulmonary Diseases, Kuopio University Hospital, Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Randell
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine and Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Virtanen
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D007073:Immunoglobulin E; C000621666:Can f 5 allergen, Canis familiaris; D017430:Prostate-Specific Antigen
keywords: Can f 5; Memory T cells; T cell epitope, allergy; Th1/Th2; immunotherapy; peptide