Definition of a minimal optimal cytotoxic T-cell epitope within the hepatitis B virus nucleocapsid protein.
Residues 11 to 27 of the hepatitis B virus nucleocapsid antigen contain a cytotoxic T-cell epitope that is recognized by cytotoxic T cells from virtually all HLA-A2-positive patients with acute hepatitis B virus infection. Using panels of truncated and overlapping peptides, we now show that the optimal amino acid sequence recognized by cytotoxic T cells is a 10-mer (residues 18 to 27) containing the predicted peptide-binding motif for HLA-A2 and that this peptide can stimulate cytotoxic T cells able to recognize endogenously synthesized hepatitis B core antigen. Since patients with chronic hepatitis B virus infection fail to mount an efficient cytotoxic T-cell response to it, this epitope might serve as the starting point for the design of synthetic peptide-based immunotherapeutic strategies to terminate persistent viral infection.
Bertoletti
A
A
Cattedra Malattie Infettive, Università di Parma, Italy.
Chisari
F V
FV
Penna
A
A
Guilhot
S
S
Galati
L
L
Missale
G
G
Fowler
P
P
Schlicht
H J
HJ
Vitiello
A
A
Chesnut
R C
RC
D000208:Acute Disease; D000595:Amino Acid Sequence; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D006509:Hepatitis B / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D006512:Hepatitis B Core Antigens; D010455:Peptides