HEPATITIS-B VIRUS SMALL SURFACE-ANTIGEN PARTICLES ARE PROCESSED IN A NOVEL ENDOSOMAL PATHWAY FOR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED EPITOPE PRESENTATION

We investigated the major histocompatibility complex (MHC) class I-res tricted presentation of an epitope of the hepatitis B virus small surf ace (S) antigen particle to cloned murine cytotoxic T lymphocytes (CTL ). Efficient L(d)-restricted presentation of the S-28-39 epitope to CT L is observed in cells of different tissue origin pulsed in vitro, eit her with the antigenic S-28-39 12-mer S-peptide, or with particulate S -antigen. The kinetics of epitope presentation differ in S-peptide-pul sed and in S-particle-pulsed cells: while a 15-min pulse with the anti genic peptide sensitizes targets for class I-restricted CTL lysis, pre sentation of S-particles requires 30-60 min to sensitize cells for CTL lysis. Uptake of antigenic material and active metabolism of the pres enting cell are required for processing of S-particles, but not for se nsitizing targets with S-peptides. Intracellular processing and presen tation of S-particles is blocked in cells treated with chloroquine, NH 4Cl, primaquine, or leupeptin, but not by treatment with cycloheximide or brefeldin A. This processing pathway operates efficiently in pepti de-transporter-deficient, L(d)-transfected T2 cells, revealing a novel endosomal/lysosomal processing pathway for class I-restricted present ation of peptides derived from exogenous S-particles.