Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules.
Exogenous Ags that are processed in vacuolar endocytic compartments are generally presented by class II MHC molecules and not class I MHC (MHC-I) molecules, which conventionally present cytoplasmic or endogenous Ags. Accordingly, i.v. immunization of C57BL/6 mice with soluble OVA did not elicit a CD8 T cell response. However, i.v. immunization with OVA coupled to Latex particles (Latex-OVA) elicited an OVA-specific CD8 T cell response in vivo (particles from 59 to 2000 nm diameter were effective). In vitro, Latex-OVA was processed by H-2b macrophages and presented by Kb at least 100- to 1000-fold more efficiently than was soluble OVA. Inhibition of phagocytosis by cytochalasin D blocked the processing of Latex-OVA, whereas processing was not blocked by Brefeldin A. Latex-OVA was presented directly by H-2b macrophages or after "regurgitation" of processed OVA peptide from viable MHC-disparate macrophages for binding to surface Kb molecules on fixed H-2b macrophages. Peptide regurgitation was observed during processing of both Latex-OVA and Salmonella typhimurium 14028s that express an OVA fusion protein (Crl-OVA). However, the regurgitation pathway was less efficient than direct processing by viable H-2b macrophages. Thus, macrophages express an alternate pathway that allows MHC-I presentation of vacuolar exogenous particulate Ags, including inert synthetic particles without lipid membranes and intravacuolar bacteria. Peptides from these Ags are released from intracellular compartments to bind to surface MHC-I molecules, but peptide-MHC-I complexes also may be generated within intracellular compartments.
Harding
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Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
Song
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D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D020126:Brefeldin A; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003517:Cyclopentanes / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011137:Polystyrenes / Q000737:chemistry; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000276:immunology
D003517:Cyclopentanes; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011137:Polystyrenes; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A; C024075:styrofoam; D010047:Ovalbumin