Selective inhibition of Ii-dependent antigen presentation by Helicobacter pylori toxin VacA.

Selective inhibition of Ii-dependent antigen presentation by Helicobacter pylori toxin VacA.
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DOI:
10.1084/jem.187.1.135
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发表时间:
1998-01-05
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Montecucco C
Montecucco C
中科院分区:
其他
文献类型:
--
作者:
Molinari M;Salio M;Galli C;Norais N;Rappuoli R;Lanzavecchia A;Montecucco C

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幽门螺杆菌慢性感染的一个主要毒力因子是一种蛋白毒素(VacA),它改变晚期内体/溶酶体前区的细胞膜运输。它在幽门螺杆菌慢性感染中的作用尚不清楚。为了测试VacA改变在溶酶体前间隔中发生的抗原处理的可能性,我们使用了成熟的抗原处理和递呈模型,该模型包括破伤风类毒素特异性人类(CD4+)T细胞,由自身抗原脉冲的Epstein-Barr病毒转化的B细胞刺激。我们发现,VacA干扰破伤风毒素和类毒素的蛋白分解过程,并特异性地抑制新合成的主要组织相容性复合体(MHC)II类介导的II依赖的抗原提呈途径,而不影响依赖于循环MHC II类的提呈途径。本研究结果表明,VacA可能通过干扰保护性免疫而促进H.Pylori的持续存在,这种毒素是研究不同的抗原提呈途径的有用工具。
A major virulence factor in the stomach chronic infection by Helicobacter pylori is a protein toxin (VacA), which alters cell membrane trafficking of late endosomal/prelysosomal compartments. Its role in the chronic infection established by H. pylori is unknown. To test the possibility that VacA alters antigen processing taking place in prelysosomal compartments, we have used the well-established model of antigen processing and presentation consisting of tetanus toxoid–specific human (CD4+) T cells stimulated by autologous antigen-pulsed Epstein-Barr virus-transformed B cells. We found that VacA interferes with proteolytic processing of tetanus toxin and toxoid and specifically inhibits the Ii-dependent pathway of antigen presentation mediated by newly synthesized major histocompatibility complex (MHC) class II, while leaving unaffected the presentation pathway dependent on recycling MHC class II. The results presented here suggest that VacA may contribute to the persistence of H. pylori by interfering with protective immunity and that this toxin is a new useful tool in the study of the different pathways of antigen presentation.
细胞毒性T淋巴细胞颗粒是分泌的溶酶体,含有穿孔蛋白和颗粒酶。
DOI: 10.1084/jem.173.5.1099
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影响因子: --
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DOI: 10.1016/0966-842x(93)90047-u
发表时间: 1993-10-01
影响因子: 15.9
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通讯作者: Blaser, M J