title: Characterization of the T-cell-mediated immune response against the Aspergillus fumigatus proteins Crf1 and catalase 1 in healthy individuals.
abstract: Invasive aspergillosis is a serious infectious complication after allogeneic stem cell transplantation. One of the strategies to improve the management of aspergillosis is the adoptive transfer of antigen-specific T cells, the success of which depends on the development of a broad repertoire of antigen-specific T cells. In this study, we identified CD4+ T cells specific for the Aspergillus proteins Crf1 and catalase 1 in 18 of 24 healthy donors by intracellular staining for interferon γ and CD154. Crf1- and catalase 1-specific T cells were selected on the basis of CD137 expression and underwent single-cell expansion. Aspergillus-specific T-cell clones mainly exhibited a T-helper cell 1 phenotype and recognized a broad variety of T-cell epitopes. Five novel Crf1 epitopes, 2 previously described Crf1 epitopes, and 30 novel catalase 1 epitopes were identified. Ultimately, by using overlapping peptides of Aspergillus fumigatus proteins, Aspergillus-specific T-cell lines that have a broad specificity and favorable cytokine profile and are suitable for adoptive T-cell therapy can be generated in vitro.
authors.affiliation: Department of Hematology, Leiden University Medical Center, C2-P, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. h.jolink@lumc.nl
authors.forename: Hetty
authors.initials: H
authors.lastname: Jolink
authors.forename: Isabelle C
authors.initials: IC
authors.lastname: Meijssen
authors.forename: Renate S
authors.initials: RS
authors.lastname: Hagedoorn
authors.forename: Mark
authors.initials: M
authors.lastname: Arentshorst
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Arend
authors.initials: A
authors.lastname: Mulder
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
mesh_terms: D000946:Antigens, Fungal / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000096:biosynthesis; D002374:Catalase / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005656:Fungal Proteins / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D013194:Staining and Labeling
chemical_list: D000946:Antigens, Fungal; D018984:Epitopes, T-Lymphocyte; D005656:Fungal Proteins; D023201:CD40 Ligand; D007371:Interferon-gamma; D002374:Catalase
keywords: Aspergillus fumigatus; Crf1; T-cell; adoptive immunotherapy; catalase 1; epitope