GLYCOSYLPHOSPHATIDYLINOSITOL-LINKED DB DOES NOT INDUCE AN INFLUENZA-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSE OR RECYCLE MEMBRANE-BOUND PEPTIDES

Major 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-2D(b) molecule expressed in transgenic mice, either transmembranous (D-b-tm) or with a glycophosphatidylinositol (GPI)-lipid anchor (D-b-GPI). The recycling capacity of peptides bound to D-b-tm and D-b-GPI was investigated using glycosylated D-b-binding glycopeptides, which were detected by flow cytometry. Only the tm form of D-b was 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 D-b-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 of certain CTL responses.