Glycosylphosphatidylinositol‐linked Dbdoes not induce an influenza‐specific cytotoxic T lymphocyte response or recycle membrane‐bound peptides

摘要

AbstractMajor histocompatibility complex (MHC) class I molecules, as well as MHC class I‐bound peptides, are known to recycle between the cell surface and an undefined, endosomal‐like compartment. Little is known about the functional significance of this process. We have explored this using two different forms of the H‐2Dbmolecule expressed in transgenic mice, either transmembranous (Db‐tm) or with a glycophosphatidylinositol (GPI)‐lipid anchor (Db‐GPI). The recycling capacity of peptides bound to Db‐tm and Db‐GPI was investigated using glycosylated Db‐binding glycopeptides, which were detected by flow cytometry. Only the tm form of Dbwas found to readily internalize and recycle glycopeptides to the cell surface. When transgenic mice were immunized with influenza A virus (PR8) strain and tested for cytotoxic T lymphocyte (CTL) responses against an immunedominant nucleoprotein epitope (366–374, ASNENMETM), onyl Db‐tm mice were found to generate specific CTL responses. The results support the idea that membrane recycling of MHC class I‐bound peptides on antigen‐presenting cells may be important for the generation