Roles of proteasomes, transporter for antigen presentation (TAP), and beta 2-microglobulin in the processing of bacterial or particulate antigens via an alternate class I MHC processing pathway.
Latex-OVA and bacteria expressing an OVA fusion protein were processed by macrophages via an alternate class I MHC (MHC-I) processing pathway to present OVA(257-264):Kb. This pathway was resistant to dipeptide aldehyde proteasome inhibitors and brefeldin A, unlike the cytosolic MHC-I pathway. TAP1-/- macrophages exhibited decreases in cell surface peptide-receptive MHC-I and binding of extracellular peptide during transient incubations. This may explain an apparent influence of TAP on alternate MHC-I processing. Alternate MHC-I processing by TAP1-/- cells was enhanced by preincubation at 26 degrees C or with beta 2-microglobulin to increase peptide-receptive MHC-I. Thus, peptides may bind to MHC-I within post-Golgi vacuolar organelles accessible to exogenous beta 2-microglobulin or on the cell surface (following peptide regurgitation).
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Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Harding
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D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000942:Antigens, Bacterial / Q000378:metabolism; D020126:Brefeldin A; D003517:Cyclopentanes / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D066298:In Vitro Techniques; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D013347:Subcellular Fractions / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000942:Antigens, Bacterial; D003517:Cyclopentanes; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin; D020126:Brefeldin A; D010047:Ovalbumin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex