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-2Db molecule 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 Db 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), only 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 of certain CTL responses.
Abdel Motal
U M
UM
Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden.
Sentman
C L
CL
Zhou
X
X
Robinson
P J
PJ
Dahmén
J
J
Jondal
M
M
D000818:Animals; D001692:Biological Transport; D003602:Cytotoxicity, Immunologic; D011992:Endosomes / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D009980:Influenza A virus / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology; D010455:Peptides / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
D017261:Glycosylphosphatidylinositols; D015395:Histocompatibility Antigens Class I; D010455:Peptides