Hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response in humans: characterization of HLA class II-restricted CTLs that recognize endogenously synthesized HBV envelope antigens.
In this study, we show that CD4+, hepatitis B virus (HBV) envelope-specific T-cell clones produced by stimulation with a particulate antigen preparation are able to recognize and kill not only autologous antigen-presenting cells incubated with exogenous HBV envelope antigens but also autologous HLA class II-positive cells expressing endogenously synthesized HBV envelope antigens following infection with recombinant vaccinia viruses or transfection with recombinant Epstein-Barr virus expression vectors. Experiments with lysosomotropic agents and brefeldin A suggest that the endosomal compartment is likely involved in the processing of endogenously synthesized viral proteins for recognition by CD4+ T cells. Our study indicates that HBV envelope-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes can potentially participate in the immune clearance of HBV-infected cells and the pathogenesis of hepatocellular injury in hepatitis B.
Penna
A
A
Cattedra Malattie Infettive, Università di Parma, Italy.
Fowler
P
P
Bertoletti
A
A
Guilhot
S
S
Moss
B
B
Margolskee
R F
RF
Cavalli
A
A
Valli
A
A
Fiaccadori
F
F
Chisari
F V
FV
D000643:Ammonium Chloride / Q000494:pharmacology; D000956:Antigens, Viral / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology; D020126:Brefeldin A; D015704:CD4 Antigens / Q000276:immunology; D002738:Chloroquine / Q000494:pharmacology; D002999:Clone Cells; D003517:Cyclopentanes / Q000494:pharmacology; D006681:HLA-D Antigens / Q000032:analysis / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000276:immunology*
D000956:Antigens, Viral; D000998:Antiviral Agents; D015704:CD4 Antigens; D003517:Cyclopentanes; D006681:HLA-D Antigens; D014759:Viral Envelope Proteins; D000643:Ammonium Chloride; D020126:Brefeldin A; D002738:Chloroquine