Salmonella regulates polyubiquitination and surface expression of MHC class II antigens
Salmonella regulates polyubiquitination and surface expression of MHC class II antigens
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DOI：
10.1073/pnas.0906735106
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发表时间：
2009-08-18
影响因子：
11.1
通讯作者：
Kelly, Adrian P.
中科院分区：
文献类型：
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作者：
Lapaque, Nicolas;Hutchinson, James L.;Kelly, Adrian P.
鼠伤寒沙门氏菌是一种兼性病原体，能够进入专职和非专职抗原呈递细胞并在其中复制。控制感染需要MHC II类限制性CD 4 T辅助细胞应答。在这里，我们表明，沙门氏菌感染诱导HLA-DR的多聚泛素化，翻译后修饰，导致从细胞表面去除成熟的，肽加载的，α-β-二聚体。未成熟的α β Ii复合物不受影响。所有II类同种型的表面表达，HLA-DP，-DQ和-DR，在感染的细胞中减少，但其他细胞表面分子的交通通过II类肽装载隔室不受影响。携带ssaV突变的沙门氏菌菌株没有诱导II类泛素化，这一过程涉及沙门氏菌T3 SS-2效应蛋白。T3 SS-2效应子，与确定或建议的作用，在泛素化，不需要II类下调，表明一个额外的T3 SS-2效应子参与调节MHC II类泛素化。虽然被认为是一种病毒免疫逃避策略，但在这里，我们证明了细菌可以通过泛素化控制表面MHC的表达。
Salmonella typhimurium is a facultative pathogen capable of entering and replicating in both professional and non-professional antigen presenting cells. Control of infection requires MHC class II restricted CD4 T-helper cell responses. Here we show that Salmonella infection induced polyubiquitination of HLA-DR, a post-translational modification that led to removal of mature, peptide loaded, alpha beta dimers from the cell surface. Immature alpha beta Ii complexes were unaffected. Surface expression of all class II isotypes, HLA-DP, -DQ, and -DR, was reduced in infected cells, but other cell-surface molecules that traffic through class II peptide loading compartments were unaffected. A Salmonella strain carrying a mutation in ssaV did not induce ubiquitination of class II, implicating Salmonella T3SS-2 effector proteins in the process. T3SS-2 effectors, with established or proposed roles in ubiquitination, were not required for class II down-regulation, suggesting that an additional T3SS-2 effector is involved in regulating MHC class II ubiquitination. Although recognized as a viral immune evasion strategy, here, we demonstrate that bacteria can control surface MHC expression through ubiquitination.