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-micron HBsAg aggregates, only macrophages (but not other cell types tested) presented the Ld-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-microns 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 immunogenicity. 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.
Schirmbeck
R
R
Institute for Medical Microbiology, University of Ulm, Germany.
Böhm
W
W
Melber
K
K
Reimann
J
J
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004705:Endocytosis / Q000276:immunology; D006511:Hepatitis B Antigens / Q000737:chemistry / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006358:Hot Temperature; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology
D006511:Hepatitis B Antigens; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins