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-restricted presentation of an epitope of the hepatitis B virus small surface (S) antigen particle to cloned murine cytotoxic T lymphocytes (CTL). Efficient Ld-restricted presentation of the S28-39 epitope to CTL is observed in cells of different tissue origin pulsed in vitro, either with the antigenic S28-39 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, NH4Cl, primaquine, or leupeptin, but not by treatment with cycloheximide or brefeldin A. This processing pathway operates efficiently in peptide-transporter-deficient, Ld-transfected T2 cells, revealing a novel endosomal/lysosomal processing pathway for class I-restricted presentation of peptides derived from exogenous S-particles.
Schirmbeck
R
R
Department Bacteriology, University of Ulm, Germany.
Melber
K
K
Reimann
J
J
D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D011992:Endosomes / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007114:Immunization; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D015395:Histocompatibility Antigens Class I