title: Activation of HIV-1 Gag-specific CD8+ T cells by yeast-derived VLP-pulsed dendritic cells is influenced by the level of mannose on the VLP antigen.
abstract: Dendritic cells (DCs) are professional antigen-presenting cells that possess a unique capacity to cross-present exogenous antigens efficiently to CD8(+) T cells. We previously demonstrated that monocyte-derived DCs (MDDCs) pulsed with yeast-derived HIV-1 Gag virus-like particles (VLPs) were able to activate Gag-specific CD8(+) T cells from HIV-1-infected individuals. Yeast VLPs are abundantly mannosylated (high-mannose type: HmVLPs) and are highly immunogenic. Because lectin receptors are shown to negatively regulate Th1 responses, we investigated the relationship between VLP mannosylation level and MDDC cross-presentation activity. Poorly mannosylated VLPs (low-mannose type: LmVLPs) were prepared using a yeast mnn9 mutant strain that lacks a core mannosylation enzyme. We found that MDDCs pulsed with LmVLPs activated Gag-specific T cells more strongly than those pulsed with HmVLPs. However, MDDCs showed similar antigen uptake and intracellular transport of both types of VLPs. Interestingly, LmVLPs induced IL-12 production slightly more than HmVLPs (yet statistically significant). Furthermore, the level of LPS-induced IL-10 production was enhanced by pulsing with HmVLPs, but not with LmVLPs. These results indicate that lectin receptors recognizing mannose may influence the Th1/Th2 balance of the immune response, resulting in reduced efficiency of CD8(+) T cell activation by a heavily mannosylated antigen presented by DCs.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1 Shinjuku-ku, Tokyo, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Mizukoshi
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yu-Ya
authors.initials: YY
authors.lastname: Mitsuki
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Terahara
authors.forename: Ai
authors.initials: A
authors.lastname: Kawana-Tachikawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Aikichi
authors.initials: A
authors.lastname: Iwamoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008358:Mannose / Q000032:analysis*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D022701:Virosomes / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D022701:Virosomes; D054301:gag Gene Products, Human Immunodeficiency Virus; D008358:Mannose