Two human immunodeficiency virus vaccinal lipopeptides follow different cross-presentation pathways in human dendritic cells
Two human immunodeficiency virus vaccinal lipopeptides follow different cross-presentation pathways in human dendritic cells
复制标题
DOI：
10.1128/jvi.77.2.1564-1570.2003
复制
发表时间：
2003-01-01
影响因子：
5.4
通讯作者：
Hosmalin, A
中科院分区：
文献类型：
--
作者：
Andrieu, M;Desoutter, JF;Hosmalin, A
针对人类免疫缺陷病毒（HIV）的有效疫苗必须诱导良好的细胞免疫反应。为此，它必须由树突状细胞进行处理和呈递，这是初级 T 淋巴细胞刺激所必需的。我们之前已经证明，含有来自HIV-1的短表位肽的模型脂肽被人树突状细胞内吞并与主要组织相容性复合物I类分子相关联呈递到特定的CD8+T淋巴细胞，但需要精确确定交叉呈递途径。我们研究了一种较长的脂肽 (Pol(461-484)) 和另一种目前用于疫苗试验的脂肽 (Nef(66-97))。与较短的脂肽一样，罗丹明标记的 Pol(461-484) 脂肽通过内吞作用内化，如通过共聚焦显微镜评估的。脂肽经树突状细胞加工后呈递给分别对 HLA-A*0201 限制性 Pol(476-484) 和 HLA-A*0301 限制性 Nef(73-82) 表位具有特异性的 CD8(+) T 细胞。两种脂肽的呈递均被布雷菲德菌素 A 抑制。Pol 脂肽的呈递被环氧霉素（一种蛋白酶体特异性抑制剂）抑制，但不被莫能菌素抑制。这表明它能够进入胞质溶胶并被蛋白酶体消化。相反，Nef脂肽的呈递不受环氧霉素抑制，但受到莫能菌素（一种酸依赖性内体酶活性的经典抑制剂）的抑制，表明内吞加工途径产生主要组织相容性复合物I类限制性呈递。因此，两种脂肽遵循不同的交叉呈递途径，均能有效呈递至CD8(+) T淋巴细胞。
An efficient vaccine against human immunodeficiency virus (HIV) must induce good cellular immune responses. To do this, it must be processed and presented by dendritic cells, which are required for primary T-lymphocyte stimulation. We have previously shown that a model lipopeptide containing a short epitopic peptide from HIV-1 was endocytosed and presented in association with major histocompatibility complex class I molecules by human dendritic cells to specific CD8(+) T lymphocytes, but the cross-presentation pathway needed to be precisely determined. We have studied a longer lipopeptide (Pol(461-484)) and another lipopeptide (Nef(66-97)) currently being used in vaccine trials. Like the shorter lipopeptide, the rhodamine-labeled Pol(461-484) lipopeptide was internalized by endocytosis, as assessed by confocal microscopy. The lipopeptides were processed by dendritic cells and presented to CD8(+) T cells specific for the HLA-A*0201-restricted Pol(476-484) and the HLA-A*0301-restricted Nef(73-82) epitope, respectively. Presentation of both lipopeptides was inhibited by brefeldin A. Presentation of the Pol lipopeptide was inhibited by epoxomycin, a proteasome-specific inhibitor, but not by monensin. This shows that it gained access to the cytosol to be digested by the proteasome. In contrast, presentation of the Nef lipopeptide was not inhibited by epoxomycin but was inhibited by monensin, a classical inhibitor of acid-dependent endosomal enzyme activity, indicating an endocytic processing pathway yielding to major histocompatibility complex class I-restricted presentation. Therefore, the two lipopeptides followed different cross-presentation pathways, both resulting in efficient presentation to CD8(+) T lymphocytes.