Hepatitis B virus small surface antigen particles are processed in a novel endosomal pathway for major histocompatibility complex class I‐restricted epitope presentation

TLDR

The study examined MHC class I presentation of a hepatitis B virus small surface antigen epitope to cloned murine cytotoxic T lymphocytes. Efficient presentation of the S28‑39 epitope to CTLs occurs via a novel endosomal/lysosomal pathway that requires antigen uptake and cell metabolism, shows faster kinetics for peptide pulsing than particle pulsing, and is inhibited by lysosomal blockers but not by protein synthesis or ER‑Golgi transport inhibitors.

Abstract

Abstract We investigated the major histocompatibility complex (MHC) class I‐restricted presentation of an epitope of the hepatitis B virus small surface (S) antigen particle to cloned murine cytotoxic T lymphocytes (CTL). Efficient L d ‐restricted presentation of the S 28–39 epitope to CTL is observed in cells of different tissue origin pulsed in vitro , either with the antigenic S 28–39 12‐mer S‐peptide, or with particulate S‐antigen. The kinetics of epitope presentation differ in S‐peptide‐pulsed and in S‐particle‐pulsed cells: while a 15‐min pulse with the antigenic peptide sensitizes targets for class I‐restricted CTL lysis, presentation of S‐particles requires 30–60 min to sensitize cells for CTL lysis. Uptake of antigenic material and active metabolism of the presenting cell are required for processing of S‐particles, but not for sensitizing targets with S‐peptides. Intracellular processing and presentation of S‐particles is blocked in cells treated with chloroquine, NH 4 Cl, primaquine, or leupeptin, but not by treatment with cycloheximide or brefeldin A. This processing pathway operates efficiently in peptide‐transporter‐deficient, L d ‐transfected T2 cells, revealing a novel endosomal/lysosomal processing pathway for class I‐restricted presentation of peptides derived from exogenous S‐particles.