Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules.
Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules.
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DOI：
10.4049/jimmunol.153.11.4925
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发表时间：
1994-12
影响因子：
4.4
通讯作者：
C. V. Harding;Rui Song
中科院分区：
文献类型：
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作者：
C. V. Harding;Rui Song
在液泡内吞区室中加工的外源性 Ag 通常由 II 类 MHC 分子呈递，而不是由 I 类 MHC (MHC-I) 分子呈递，后者通常呈递细胞质或内源性 Ag。因此，静脉注射。用可溶性 OVA 免疫 C57BL/6 小鼠并未引发 CD8 T 细胞反应。然而，静脉注射。使用与乳胶颗粒偶联的 OVA (Latex-OVA) 进行免疫在体内引发了 OVA 特异性 CD8 T 细胞反应（直径 59 至 2000 nm 的颗粒有效）。在体外，Latex-OVA 由 H-2b 巨噬细胞加工并由 Kb 呈递，其效率比可溶性 OVA 至少高 100 至 1000 倍。细胞松弛素 D 对吞噬作用的抑制阻断了 Latex-OVA 的加工，而布雷菲德菌素 A 则不会阻断加工。 Latex-OVA 直接由 H-2b 巨噬细胞呈递，或者在来自活的 MHC 不同巨噬细胞的加工过的 OVA 肽“回流”后与固定的 H-2b 巨噬细胞上的表面 Kb 分子结合。在表达 OVA 融合蛋白 (Crl-OVA) 的 Latex-OVA 和鼠伤寒沙门氏菌 14028s 的加工过程中观察到肽反流。然而，反流途径的效率低于活 H-2b 巨噬细胞的直接处理。因此，巨噬细胞表达另一种途径，允许 MHC-I 呈递液泡外源颗粒 Ag，包括没有脂质膜的惰性合成颗粒和液泡内细菌。来自这些 Ag 的肽从细胞内区室释放以与表面 MHC-I 分子结合，但肽-MHC-I 复合物也可能在细胞内区室内产生。
Exogenous Ags that are processed in vacuolar endocytic compartments are generally presented by class II MHC molecules and not class I MHC (MHC-I) molecules, which conventionally present cytoplasmic or endogenous Ags. Accordingly, i.v. immunization of C57BL/6 mice with soluble OVA did not elicit a CD8 T cell response. However, i.v. immunization with OVA coupled to Latex particles (Latex-OVA) elicited an OVA-specific CD8 T cell response in vivo (particles from 59 to 2000 nm diameter were effective). In vitro, Latex-OVA was processed by H-2b macrophages and presented by Kb at least 100- to 1000-fold more efficiently than was soluble OVA. Inhibition of phagocytosis by cytochalasin D blocked the processing of Latex-OVA, whereas processing was not blocked by Brefeldin A. Latex-OVA was presented directly by H-2b macrophages or after "regurgitation" of processed OVA peptide from viable MHC-disparate macrophages for binding to surface Kb molecules on fixed H-2b macrophages. Peptide regurgitation was observed during processing of both Latex-OVA and Salmonella typhimurium 14028s that express an OVA fusion protein (Crl-OVA). However, the regurgitation pathway was less efficient than direct processing by viable H-2b macrophages. Thus, macrophages express an alternate pathway that allows MHC-I presentation of vacuolar exogenous particulate Ags, including inert synthetic particles without lipid membranes and intravacuolar bacteria. Peptides from these Ags are released from intracellular compartments to bind to surface MHC-I molecules, but peptide-MHC-I complexes also may be generated within intracellular compartments.