R. Schirmbeck et al., PROCESSING OF EXOGENOUS HEAT-AGGREGATED (DENATURED) AND PARTICULATE (NATIVE) HEPATITIS-B SURFACE-ANTIGEN FOR CLASS I-RESTRICTED EPITOPE PRESENTATION, The Journal of immunology, 155(10), 1995, pp. 4676-4684
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.