title: Calnexin induces expansion of antigen-specific CD4(+) T cells that confer immunity to fungal ascomycetes via conserved epitopes.
abstract: Fungal infections remain a threat due to the lack of broad-spectrum fungal vaccines and protective antigens. Recent studies showed that attenuated Blastomyces dermatitidis confers protection via T cell recognition of an unknown but conserved antigen. Using transgenic CD4(+) T cells recognizing this antigen, we identify an amino acid determinant within the chaperone calnexin that is conserved across diverse fungal ascomycetes. Calnexin, typically an ER protein, also localizes to the surface of yeast, hyphae, and spores. T cell epitope mapping unveiled a 13-residue sequence conserved across Ascomycota. Infection with divergent ascomycetes, including dimorphic fungi, opportunistic molds, and the agent causing white nose syndrome in bats, induces expansion of calnexin-specific CD4(+) T cells. Vaccine delivery of calnexin in glucan particles induces fungal antigen-specific CD4(+) T cell expansion and resistance to lethal challenge with multiple fungal pathogens. Thus, the immunogenicity and conservation of calnexin make this fungal protein a promising vaccine target.
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Marcel
authors: M
authors: Wüthrich
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Tristan T
authors: TT
authors: Brandhorst
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Thomas D
authors: TD
authors: Sullivan
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Hanna
authors: H
authors: Filutowicz
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Alana
authors: A
authors: Sterkel
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Douglas
authors: D
authors: Stewart
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Mengyi
authors: M
authors: Li
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Tassanee
authors: T
authors: Lerksuthirat
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
authors: Vanessa
authors: V
authors: LeBert
authors: University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Zu Ting
authors: ZT
authors: Shen
authors: University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Gary
authors: G
authors: Ostroff
authors: University of Cincinnati College of Medicine and Veterans Affairs Hospital, Cincinnati, OH 45221, USA.
authors: George S
authors: GS
authors: Deepe
authors: University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors: Chiung Yu
authors: CY
authors: Hung
authors: University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors: Garry
authors: G
authors: Cole
authors: University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors: Jennifer A
authors: JA
authors: Walter
authors: University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors: Marc K
authors: MK
authors: Jenkins
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA; Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA. Electronic address: bsklein@wisc.edu.
authors: Bruce
authors: B
authors: Klein
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology*; D001203:Ascomycota / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D037281:Calnexin / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects*; D000939:Epitopes / Q000276:immunology*; D051379:Mice
chemical_list: D000946:Antigens, Fungal; D000939:Epitopes; D037281:Calnexin