Inhibition of cell surface MHC class II expression by Salmonella
Inhibition of cell surface MHC class II expression by Salmonella
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DOI：
10.1002/eji.200425314
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发表时间：
2004-09-01
影响因子：
5.4
通讯作者：
Trowsdale, J
中科院分区：
文献类型：
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作者：
Mitchell, EK;Mastroeni, P;Trowsdale, J
主要组织相容性复合体（MHC）分子呈递肽段是适应性免疫应答的重要组成部分。为了在宿主内持续存在，许多病原体进化出了干扰MHC抗原呈递的策略。我们发现，在含有细胞内沙门氏菌的人类细胞中，MHC II类分子在细胞表面的表达显著降低。这种影响对MHC II类分子具有特异性，因为其他表面受体的表达保持不变。我们研究了潜在机制，发现II类分子的生物合成和肽段加载不受沙门氏菌存在的影响；然而，感染导致成熟分子在细胞内积累。细胞内的II类分子与溶酶体相关膜蛋白 - 1和人类白细胞抗原 - DM共定位，但不与含沙门氏菌的液泡共定位。利用在沙门氏菌致病岛 - 2型III型分泌系统的不同组分和效应因子方面有缺陷的沙门氏菌突变体，我们将对II类分子的影响追溯到sifA基因座。已表明SifA参与为含沙门氏菌的液泡募集膜。我们的数据表明SifA在干扰MHC II类抗原呈递方面具有额外的作用。
Peptide presentation by MHC molecules is an essential component of the adaptive immune response. To persist in a host, many pathogens have evolved strategies that interfere with MHC antigen-presentation. We show that in human cells harboring intracellular Salmonella, MHC class II cell surface expression was substantially reduced. The effect was specific for MHC class II as expression of additional surface receptors remained unchanged. We investigated the underlying mechanism and showed that class II biosynthesis and peptide loading were unaffected by the presence of Salmonella; however, infection led to an intracellular accumulation of mature molecules. The intracellular class II colocalized with lysosome-associated membrane protein-1 and HLA-DM but not with the Salmonella-containing vacuole. Using Salmonella mutants defective in different components and effectors of the Salmonella pathogenicity island-2 type-III secretion system, we traced the effect on class II to the sifA locus. SifA has been shown to be involved in recruiting membrane for the Salmonella-containing vacuoles. Our data suggest an additional role for SifA in interfering with MHC class II antigen-presentation.