Bacterial proteins can be processed by macrophages in a transporter associated with antigen processing-independent, cysteine protease-dependent manner for presentation by MHC class I molecules.
MHC class I molecules present peptides derived primarily from endogenously synthesized proteins on the cell surface as ligands for CD8+ T cells. However, CD8+ T cell responses to extracellular bacteria, virus-infected, or tumor cells can also be elicited because certain professional APC can generate peptide/MHC class I (MHC-I) complexes from exogenous sources. Whether the peptide/MHC-I complexes are generated because the exogenous proteins enter the classical cytosolic, TAP-dependent MHC-I processing pathway or an alternate pathway is controversial. Here we analyze the generation of peptide/MHC-I complexes from recombinant Escherichia coli as an exogenous Ag source that could be delivered to the phagosomes or directly into the cytosol. We show that peritoneal and bone marrow macrophages generate peptide/MHC-I complexes by the classical as well as an alternate, but relatively less efficient, TAP-independent pathway. Using a novel method to detect proteolytic intermediates we show that the generation of the optimal MHC-I binding peptide in the alternate pathway requires cysteine as well as other protease(s). This alternate TAP-independent pathway also operates in vivo and provides a potential mechanism for eliciting CD8+ T cell responses to exogenous Ags.
Campbell
D J
DJ
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Serwold
T
T
Shastri
N
N
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D029968:Escherichia coli Proteins; D005260:Female; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D058619:Maltose-Binding Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D006183:H-2 Antigens; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D009842:Oligopeptides; D010455:Peptides; D011993:Recombinant Fusion Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C461599:maltose transport system, E coli; D010047:Ovalbumin; D003546:Cysteine Endopeptidases