MHC I presentation of Toxoplasma gondii immunodominant antigen does not require Sec22b and is regulated by antigen orientation at the vacuole membrane
MHC I presentation of Toxoplasma gondii immunodominant antigen does not require Sec22b and is regulated by antigen orientation at the vacuole membrane
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DOI：
10.1002/eji.201646859
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发表时间：
2017-07-01
影响因子：
5.4
通讯作者：
Blanchard, Nicolas
中科院分区：
文献类型：
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作者：
Buaillon, Celia;Guerrero, Nestor A.;Blanchard, Nicolas
细胞内弓形虫寄生虫在寄生虫液泡（PV）内复制。T.弓形虫分泌的蛋白质在PV空间中保持可溶性，插入PV膜或输出到PV边界之外。除了支持T。在弓形虫生长过程中，这些蛋白质可以被MHC I加工和呈递，用于CD 8（+）T细胞识别。然而，目前还不清楚膜结合是否影响所采用的加工途径，以及膜抗原的拓扑结构是否影响其MHC I呈递。在这里，我们报告的可溶性和膜结合抗原的MHC I途径不同，在他们的要求为主机ER招聘。与可溶性SAG 1-OVA模型抗原相比，我们发现膜结合GRA 6的呈递独立于SNARE Sec 22 b，后者是将宿主内质网组分转移到PV上的关键分子。使用寄生虫修改分泌跨膜抗原与相反的方向，我们进一步表明，MHC I的介绍是非常有利的C-末端表位暴露于宿主细胞胞质溶胶，这对应于GRA 6的自然方向时。我们的数据表明，细胞内病原体释放的抗原的生物化学性质决定性地指导它们的加工途径，并且是考虑疫苗接种策略的有价值的参数。
The intracellular Toxoplasma gondii parasite replicates within a parasitophorous vacuole (PV). T. gondii secretes proteins that remain soluble in the PV space, are inserted into PV membranes or are exported beyond the PV boundary. In addition to supporting T. gondii growth, these proteins can be processed and presented by MHC I for CD8(+) T-cell recognition. Yet it is unclear whether membrane binding influences the processing pathways employed and if topology of membrane antigens impacts their MHC I presentation. Here we report that the MHC I pathways of soluble and membrane-bound antigens differ in their requirement for host ER recruitment. In contrast to the soluble SAG1-OVA model antigen, we find that presentation of the membrane-bound GRA6 is independent from the SNARE Sec22b, a key molecule for transfer of host endoplasmic reticulum components onto the PV. Using parasites modified to secrete a transmembrane antigen with opposite orientations, we further show that MHC I presentation is highly favored when the C-terminal epitope is exposed to the host cell cytosol, which corresponds to GRA6 natural orientation. Our data suggest that the biochemical properties of antigens released by intracellular pathogens critically guide their processing pathway and are valuable parameters to consider for vaccination strategies.