Purification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes.
In vitro studies in patients with hepatitis B virus (HBV) infection have suggested that hepatocytolysis induced by CD8+ cytotoxic T lymphocytes (CTLs) is the most important effector pathway in eliminating infected cells. The recognition is implicated in the endogenously processed HBV antigens in the context of HLA class I molecules presented on the liver cell membrane. However, the naturally occurring HBV peptide antigens have not yet been demonstrated. We report here that a naturally processed peptide antigen P2 was isolated from HLA class I molecules of HBV-infected liver cell membrane. The P2 peptide exhibited the activity of sensitizing target cells for lysis by CD8+ CTLs. The P2 sequence (YVNVNMGLK) purified from liver tissue was in concordance with that encoded by the viral genome for the HBV nucleocapsid antigen or HBcAg 88-96. P2 peptide could also be isolated from the EBV-transformed B cells that were transfected by HBcAg-expressing vector. The P2 epitope, sharing the HLA-A11 binding motifs, was recognized by HLA-A11-restricted CD8+ CTLs. The data provided direct evidence that, in hepatitis B patients, antigenic peptides of HBV were processed by hepatocytes, presented with the class I MHC molecules, and recognized by CD8+ CTLs.
Tsai
S L
SL
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung Medical College, Taipei, Taiwan.
Chen
M H
MH
Yeh
C T
CT
Chu
C M
CM
Lin
A N
AN
Chiou
F H
FH
Chang
T H
TH
Liaw
Y F
YF
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000382:microbiology; D000939:Epitopes; D015234:HLA-A Antigens / Q000276:immunology; D059870:HLA-A11 Antigen; D006511:Hepatitis B Antigens / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011499:Protein Processing, Post-Translational; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D006511:Hepatitis B Antigens; D006512:Hepatitis B Core Antigens; D010455:Peptides