Viral and bacterial minigene products are presented by MHC class I molecules with similar efficiencies.
MHC class I molecules present short peptides, usually 8-10 amino acids in length, to CD8(+) T cells. These peptides are typically generated from full-length endogenously synthesized proteins degraded by the antigen processing machinery of the target cell. However, exogenous proteins, whether originating from intracellular bacteria or parasites or via phagocytosis during cross-presentation, can also be processed for presentation by MHC class I molecules. It is currently not known whether endogenously synthesized proteins and proteins acquired from exogenous sources follow the same presentation pathway. One clue that the processing pathways followed by endogenous and exogenous proteins may not be identical is the vastly different presentation efficiencies reported for viral versus bacterial antigens. Because class I antigen processing involves multiple steps, we sought to determine where in the processing pathway these differences in efficiency occur. To accomplish this, we expressed identical minimal peptide determinants from viral and bacterial vectors using a minigene expression system and determined the rate of peptide-MHC generation per molecule of minigene product synthesized. We found that peptides expressed from either the viral or bacterial vector were presented with virtually identical efficiencies. These results suggest that differences in the processing pathways followed by endogenous versus exogenous proteins most likely occur at a point prior to where free peptide is liberated from full-length protein.
Department of Microbiology and Immunology, SUNY Upstate Medical University, 750 E Adams St, 2285 Weiskotten Hall Addition, Syracuse, NY 13210, United States.
Benjamin J
BJ
Wolf
Michael F
MF
Princiotta
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003600:Cytosol / Q000378:metabolism; D005798:Genes, Bacterial / Q000235:genetics*; D005814:Genes, Viral / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008087:Listeria / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014176:Protein Biosynthesis; D011995:Recombination, Genetic; D013499:Surface Properties; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D000942:Antigens, Bacterial; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D046988:Proteasome Endopeptidase Complex