PMID- 19059495 OWN - NLM STAT- MEDLINE DCOM- 20090605 LR - 20161020 IS - 1769-714X (Electronic) IS - 1286-4579 (Linking) VI - 11 IP - 2 DP - 2009 Feb TI - 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. PG - 191-7 LID - 10.1016/j.micinf.2008.11.004 [doi] AB - 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. FAU - Mizukoshi, Fuminori AU - Mizukoshi F AD - Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1 Shinjuku-ku, Tokyo, Japan. FAU - Yamamoto, Takuya AU - Yamamoto T FAU - Mitsuki, Yu-Ya AU - Mitsuki YY FAU - Terahara, Kazutaka AU - Terahara K FAU - Kawana-Tachikawa, Ai AU - Kawana-Tachikawa A FAU - Kobayashi, Kazuo AU - Kobayashi K FAU - Iwamoto, Aikichi AU - Iwamoto A FAU - Morikawa, Yuko AU - Morikawa Y FAU - Tsunetsugu-Yokota, Yasuko AU - Tsunetsugu-Yokota Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081124 PL - France TA - Microbes Infect JT - Microbes and infection JID - 100883508 RN - 0 (Virosomes) RN - 0 (gag Gene Products, Human Immunodeficiency Virus) RN - PHA4727WTP (Mannose) SB - IM MH - CD8-Positive T-Lymphocytes/*immunology MH - Cells, Cultured MH - Dendritic Cells/*immunology MH - HIV-1/*immunology MH - Humans MH - Mannose/*analysis MH - Saccharomyces cerevisiae/genetics/metabolism MH - Virosomes/*chemistry/genetics/*immunology MH - gag Gene Products, Human Immunodeficiency Virus/genetics/*immunology EDAT- 2008/12/09 09:00 MHDA- 2009/06/06 09:00 CRDT- 2008/12/09 09:00 PHST- 2008/10/03 00:00 [received] PHST- 2008/11/10 00:00 [revised] PHST- 2008/11/12 00:00 [accepted] PHST- 2008/12/09 09:00 [pubmed] PHST- 2009/06/06 09:00 [medline] PHST- 2008/12/09 09:00 [entrez] AID - S1286-4579(08)00310-9 [pii] AID - 10.1016/j.micinf.2008.11.004 [doi] PST - ppublish SO - Microbes Infect. 2009 Feb;11(2):191-7. doi: 10.1016/j.micinf.2008.11.004. Epub 2008 Nov 24.