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The Journal of Immunology, Vol 153, Issue 11 4925-4933, Copyright © 1994 by American Association of Immunologists

ARTICLES

Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules

CV Harding and R Song
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.

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.


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