PHAGOCYTIC PROCESSING OF EXOGENOUS PARTICULATE ANTIGENS BY MACROPHAGES FOR PRESENTATION BY CLASS-I MHC MOLECULES

Exogenous Ags that are processed in vacuolar endocytic compartments ar e generally presented by class II MHC molecules and not class I MHC (M HC-I) molecules, which conventionally present cytoplasmic or endogenou s 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 C D8 T cell response in vivo (particles from 59 to 2000 nm diameter were effective). In vitro, Latex-OVA was processed by H-2(b) macrophages a nd presented by K-b at least 100- to 1000-fold more efficiently than w as soluble OVA. Inhibition of phagocytosis by cytochalasin D blocked t he processing of Latex-OVA, whereas processing was not blocked by Bref eldin A, Latex-OVA was presented directly by H-2(b) macrophages or aft er ''regurgitation'' of processed OVA peptide from viable MHC-disparat e macrophages for binding to surface K-b molecules on fixed H-2(b) mac rophages. Peptide regurgitation was observed during processing of both Latex-OVA and Salmonella typhimurium 14028s that express an OVA fusio n protein (Crl-OVA). However, the regurgitation pathway was less effic ient than direct processing by viable H-2(b) macrophages. Thus, macrop hages express an alternate pathway that allows MHC-I presentation of v acuolar exogenous particulate Ags, including inert synthetic particles without lipid membranes and intravacuolar bacteria. Peptides from the se Ags are released from intracellular compartments to bind to surface MHC-I molecules, but peptide-MHC-I complexes also may be generated wi thin intracellular compartments.