1. Calnexin Induces Expansion of Antigen-Specific CD4+ T Cells that Confer Immunity to Fungal Ascomycetes via Conserved Epitopes
- Author
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Marc K. Jenkins, George S. Deepe, Hanna I. Filutowicz, Mengyi Li, Bruce S. Klein, Marcel Wüthrich, Jennifer A Walter, Alana K. Sterkel, Tassanee Lerksuthirat, Douglas Stewart, Vanessa LeBert, T. Tristan Brandhorst, Gary R. Ostroff, Garry T. Cole, Zu Ting Shen, Thomas D. Sullivan, and Chiung Yu Hung
- Subjects
CD4-Positive T-Lymphocytes ,Cancer Research ,Antigens, Fungal ,Calnexin ,Microbiology ,Epitope ,Epitopes ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Ascomycota ,Antigen ,Immunology and Microbiology(all) ,Virology ,Animals ,Molecular Biology ,Cell Proliferation ,030304 developmental biology ,Fungal vaccine ,0303 health sciences ,Fungal protein ,biology ,Immunogenicity ,biology.organism_classification ,Epitope mapping ,Parasitology ,030215 immunology - Abstract
Summary 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.
- Published
- 2015
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