Mizukoshi Fuminori, Yamamoto Takuya, Mitsuki Yu-Ya, Terahara Kazutaka, Kawana-Tachikawa Ai, Kobayashi Kazuo, Iwamoto Aikichi, Morikawa Yuko, Tsunetsugu-Yokota Yasuko
Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1 Shinjuku-ku, Tokyo, Japan.
Microbes Infect. 2009 Feb;11(2):191-7. doi: 10.1016/j.micinf.2008.11.004. Epub 2008 Nov 24.
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.
树突状细胞（DCs）是专职抗原呈递细胞，具有将外源性抗原有效交叉呈递给CD8(+) T细胞的独特能力。我们之前证明，用酵母衍生的HIV-1 Gag病毒样颗粒（VLPs）脉冲处理的单核细胞衍生DCs（MDDCs）能够激活来自HIV-1感染个体的Gag特异性CD8(+) T细胞。酵母VLPs大量被甘露糖基化（高甘露糖型：HmVLPs），且具有高度免疫原性。由于凝集素受体显示出对Th1反应有负调节作用，我们研究了VLP甘露糖基化水平与MDDC交叉呈递活性之间的关系。使用缺乏核心甘露糖基化酶的酵母mnn9突变株制备了甘露糖基化程度低的VLPs（低甘露糖型：LmVLPs）。我们发现，用LmVLPs脉冲处理的MDDCs比用HmVLPs脉冲处理的MDDCs更强烈地激活Gag特异性T细胞。然而，MDDCs对两种类型的VLPs显示出相似的抗原摄取和细胞内转运。有趣的是，LmVLPs诱导IL-12产生比HmVLPs略多（但具有统计学意义）。此外，用HmVLPs脉冲处理可增强LPS诱导的IL-10产生水平，但用LmVLPs脉冲处理则不然。这些结果表明，识别甘露糖的凝集素受体可能影响免疫反应的Th1/Th2平衡，导致DC呈递的高度甘露糖基化抗原激活CD8(+) T细胞的效率降低。
