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 surf ace 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 pro teolysis in an endocytic compartment, was insensitive to brefeldin A a nd cycloheximide, and did not involve regurgitation of antigenic pepti des. In contrast, after an in vitro pulse of cells with exogenous, hea t-denatured 1-mu m HBsAg aggregates; only macrophages (but not other c ell types tested) presented the L(d)-restricted HBsAg epitope efficien tly to CTL. Processing of exogenous HBsAg aggregates required its cyto chalasin B-sensitive uptake, was insensitive to brefeldin A, and invol ved regurgitation of antigenic peptides. Processing of the two differe nt, exogenous HBsAg preparations for class I-restricted epitope presen tation thus involved alternative pathways: an ''endocytic pathway'' fo r native 22-nm particles, and a ''phagocytic pathway'' for denatured 1 -mu m aggregates. Both HBsAg preparations displayed different immunoge nicity for class I-restricted CTL in vivo when delivered without adjuv ants: native HBsAg particles were of high immunogenicity, and denature d HBsAg aggregates were of low immogenicity. Class I-restricted CTL ar e thus primed in vivo after ''endocytic processing'' of native HBsAg p articles as well as ''phagocytic processing'' of denatured HBsAg aggre gates.