EFFICIENT MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PRESENTATION OF EXOGENOUS ANTIGEN UPON PHAGOCYTOSIS BY MACROPHAGES
EFFICIENT MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PRESENTATION OF EXOGENOUS ANTIGEN UPON PHAGOCYTOSIS BY MACROPHAGES
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DOI：
10.1073/pnas.90.11.4942
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发表时间：
1993-06-01
影响因子：
11.1
通讯作者：
ROCK, KL
中科院分区：
文献类型：
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作者：
KOVACSOVICSBANKOWSKI, M;CLARK, K;ROCK, KL
细胞外液中的抗原可以通过抗原呈递细胞（APC）的亚群加工并呈递主要组织相容性复合物（MHC）I类分子。连接到珠的鸡蛋卵清蛋白（Ova）与MHC I类分子一起由这些细胞呈递，其效率比可溶性Ova高10（4）倍。这种增强的介绍，观察与共价或非共价连接的卵和珠的不同组合物。这些缀合物的活性的关键参数是珠粒的大小。负责这种形式呈递的APC是巨噬细胞。这些细胞通过吞噬作用内化抗原构建体，因为细胞松弛素B抑制呈递。抗原的加工和与MHC I类分子的结合似乎发生在细胞内，因为在没有可检测的肽释放到细胞外液中的条件下观察到呈递。当在C57 BL/6小鼠体内注射时，Ova珠而不是可溶性Ova引发CD 4-CD 8+细胞毒性T淋巴细胞（CTL）。在用β-半乳糖苷酶珠免疫的BALB/c小鼠中获得了类似的结果。这些研究结果的影响，刺激CTL免疫的非活疫苗的发展进行了讨论。
Antigens in extracellular fluids can be processed and presented with major histocompatibility complex (MHC) class I molecules by a subset of antigen presenting cells (APCs). Chicken egg ovalbumin (Ova) linked to beads was presented with MHC class I molecules by these cells up to 10(4)-fold more efficiently than soluble Ova. This enhanced presentation was observed with covalently or noncovalently linked Ova and with beads of different compositions. A key parameter in the activity of these conjugates was the size of the beads. The APC that is responsible for this form of presentation is a macrophage. These cells internalize the antigen constructs through phagocytosis, since cytochalasin B inhibited presentation. Processing of the antigen and association with MHC class I molecules appears to occur intracellularly as presentation was observed under conditions where there was no detectable release of peptides into the extracellular fluids. When injected in vivo in C57BL/6 mice, Ova-beads, but not soluble Ova, primed CD4- CD8+ cytotoxic T lymphocytes (CTLs). Similar results were obtained in BALB/c mice immunized with beta-galactosidase-beads. The implications of these findings for development of nonliving vaccines that stimulate CTL immunity are discussed.