Differential Requirements for Endosomal Reduction in the Presentation of Two H2-Ed-Restricted Epitopes from Influenza Hemagglutinin

摘要: We examined the role of reduction in presentation two H2-E d -restricted epitopes (site 1 epitope (S1) and site 3 (S3)) occupying distinct domains influenza hemagglutinin major subunit that contains four intrachain disulfide bonds is connected to virion by one interchain bond. S3 situated within stalk region unfolds response mild acidification, loads onto recycling early endosome, while S1, located structurally constrained globular domain, nascent late endosome. Predicting dependence upon for either seemed plausible but results from several approaches were clear: S1 not dependent. Surprisingly, IFN-γ-inducible lysosomal thiol reductase (GILT), only thus far known be involved MHC class II-restricted processing, necessary generation S1. However, GILT when virus pretreated with a reducible cross-linker. The suggest unfolding Ag, perhaps prerequisite proteolytic processing many cases, proceeds spontaneously endosome or via later They further imply mechanisms GILT-independent being reserved more intractable Ags.