PROCESSING OF EXOGENOUS HEAT-AGGREGATED (DENATURED) AND PARTICULATE (NATIVE) HEPATITIS-B SURFACE-ANTIGEN FOR CLASS I-RESTRICTED EPITOPE PRESENTATION

Many cell types efficiently present an epitope of the hepatitis B surface Ag (HBsAg) to murine class I-restricted CTL following an in vitro pulse with native 22-nm HBsAg particles. Processing of exogenous HBsAg particles required its cytochalasin B-insensitive uptake and acid proteolysis in an endocytic compartment, was insensitive to brefeldin A and cycloheximide, and did not involve regurgitation of antigenic peptides. In contrast, after an in vitro pulse of cells with exogenous, heat-denatured 1-mu m HBsAg aggregates; only macrophages (but not other cell types tested) presented the L(d)-restricted HBsAg epitope efficiently to CTL. Processing of exogenous HBsAg aggregates required its cytochalasin B-sensitive uptake, was insensitive to brefeldin A, and involved regurgitation of antigenic peptides. Processing of the two different, exogenous HBsAg preparations for class I-restricted epitope presentation thus involved alternative pathways: an ''endocytic pathway'' for native 22-nm particles, and a ''phagocytic pathway'' for denatured 1-mu m aggregates. Both HBsAg preparations displayed different immunogenicity for class I-restricted CTL in vivo when delivered without adjuvants: native HBsAg particles were of high immunogenicity, and denatured HBsAg aggregates were of low immogenicity. Class I-restricted CTL are thus primed in vivo after ''endocytic processing'' of native HBsAg particles as well as ''phagocytic processing'' of denatured HBsAg aggregates.