title: Uptake of various yeast genera by antigen-presenting cells and influence of subcellular antigen localization on the activation of ovalbumin-specific CD8 T lymphocytes.
abstract: Yeasts of the genus Saccharomyces expressing recombinant antigens are currently evaluated as candidate T cell vaccines. Here, we compared the interaction kinetics between four biotechnologically relevant yeast genera (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces lactis and Pichia pastoris) and human dendritic cells as well as the involvement of Dectin-1 and mannose receptor in phagocytosis. Further, we analyzed the activation capacity of recombinant yeasts expressing ovalbumin (OVA) either intracellular, extracellular or surface-displayed by OVA-specific CD8 T lymphocytes. We found that the kinetic patterns of yeast uptake by phagocytic cells varied between the tested yeast genera and that both genus and subcellular OVA antigen localization influenced the strength of T cell activation. In particular, in S. cerevisiae, a secreted antigen was less effectively delivered than its cytosolic variant, whereas most efficient antigen delivery with P. pastoris was obtained by cell surface bound antigen. Our data indicate that protein secretion might not be an effective delivery pathway in yeast.
authors.affiliation: Molecular and Cell Biology, Saarland University, D-66123 Saarbrücken, Germany.
authors.forename: Silvia Boschi
authors.initials: SB
authors.lastname: Bazan
authors.forename: Gernot
authors.initials: G
authors.lastname: Geginat
authors.forename: Tanja
authors.initials: T
authors.lastname: Breinig
authors.forename: Manfred J
authors.initials: MJ
authors.lastname: Schmitt
authors.forename: Frank
authors.initials: F
authors.lastname: Breinig
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D004337:Drug Carriers; D005657:Fungal Vaccines / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D015003:Yeasts / Q000235:genetics / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D005657:Fungal Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D010047:Ovalbumin