Recognition of a sequestered self peptide by influenza virus-specific CD8+ cytolytic T lymphocytes.
The Ag receptors on CD8+ CTL recognize foreign antigenic peptides associated with cell surface MHC class I molecules. Peptides derived from self proteins are also normally presented by MHC class I molecules. Here we report that an H-2Kd-restricted murine CD8+ CTL clone directed to an influenza hemagglutinin epitope can recognize a peptide derived from the murine mitochondrial aconitase enzyme in association with H-2Kd molecules. Surprisingly, this self peptide is not normally displayed on the cell surface associated with the restricting MHC class I molecule. Several lines of evidence suggest that this self peptide, although requiring association with the Kd molecule for CTL recognition, is not associated with this or other MHC class I allele under physiologic conditions in intact cells. Rather, it is sequestered in the cytoplasm associated with a carrier protein and is released only upon cell disruption. These results suggest a means of restricting the entry of self peptide into the class I pathway. In addition, this finding raises the possibility that self peptides sequestered within the cell can, after release from damaged cells, interact with MHC class I molecules on bystander cells and trigger autoimmune injury by virus-specific CTLs during viral infection.
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Beirne B. Carter Center for Immunology Research, Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
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D000154:Aconitate Hydratase / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009842:Oligopeptides; D000154:Aconitate Hydratase