Up-regulation of MHC class I by flavivirus-induced peptide translocation into the endoplasmic reticulum.
Flavivirus infection of mammalian cells increases the cell surface expression of major histocompatibility complex (MHC) class I molecules, the recognition elements for cytotoxic T cells. Here, we show that the mechanism for flavivirus-induced up-regulation of class I MHC involves an increase in peptide supply to the endoplasmic reticulum. Flavivirus-mediated peptide supply for MHC class I assembly is independent of the peptide transporters for class I antigen presentation, since infection of class I MHC peptide transport-deficient cell lines with flaviviruses results in the cell surface expression of biologically functional class I MHC peptide complexes. The flavivirus-induced supply of antigenic peptides to the endoplasmic reticulum is not restricted to flavivirus-encoded peptides and independent of interferon. The data imply that peptide availability regulates surface expression of class I MHC restriction elements and suggests a mechanism for flavivirus-induced immunopathology.
Müllbacher
A
A
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Lobigs
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M
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002478:Cells, Cultured; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D018177:Flavivirus Infections / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D066298:In Vitro Techniques; D007372:Interferons / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D010455:Peptides; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D007372:Interferons