Differential antigen-processing pathways of the hepatitis B virus e and core proteins.
OBJECTIVE
Hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg) seem to play different roles in the induction and regulation of the antiviral immune response, although the two antigens share all major CD4(+) T-cell epitopes, and these epitopes can be processed from both antigens via the exogenous antigen-presenting pathway. The aim of this study was to test the ability of antigen-presenting cells to present epitopes from endogenously synthesized HBcAg/HBeAg on HLA class II molecules.


METHODS
Lymphoblastoid cell lines infected with recombinant vaccinia viruses containing various HBcAg or HBeAg constructs and stable transfectants were tested for their ability to stimulate HBcAg/HBeAg-specific CD4(+) T-cell clones.


RESULTS
Only antigen-presenting cells infected with HBeAg constructs but not those infected with HBcAg constructs were able to stimulate HBcAg/HBeAg-specific CD4(+) T-cell clones. T-cell activation by HBeAg constructs was completely inhibited by brefeldin A but not affected by chloroquin. In contrast, T-cell activation by exogenous, recombinant HBcAg was inhibited by chloroquin but not by brefeldin A.


CONCLUSIONS
The findings indicate that processing and HLA class II-associated presentation of endogenously synthesized HBeAg in virus-infected cells, including hepatocytes, may occur. This mechanism may be involved in the regulation of the CD4(+) T-cell response to HBcAg/HBeAg.
Diepolder
H M
HM
Department of Medicine II, Klinikum Grobetahadern, University of Munich, Munich, Germany.
Ries
G
G
Jung
M C
MC
Schlicht
H J
HJ
Gerlach
J T
JT
Gr ner
N
N
Caselmann
W H
WH
Pape
G R
GR
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D020126:Brefeldin A / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002738:Chloroquine / Q000494:pharmacology; D002999:Clone Cells; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology
D000939:Epitopes; D006681:HLA-D Antigens; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D011994:Recombinant Proteins; D020126:Brefeldin A; D002738:Chloroquine