Characterization of HLA DR13-restricted CD4(+) T cell epitopes of hepatitis B core antigen associated with self-limited, acute hepatitis B.
The HLA DR13 allele has been associated with a self-limited course of hepatitis B virus infection, possibly through the induction of a more vigorous hepatitis B core antigen (HBcAg) and/or hepatitis B e antigen-specific CD4(+) T cell response. HBcAg-specific CD4(+) T cell responses were investigated in three HLA DR13-positive subjects with self-limited, acute hepatitis B. HBcAg-specific, short-term T cell lines derived from these three subjects showed a dominant recognition of HBcAg peptides spanning aa 1-20 (P1), 11-30 (P2), 41-60 (P5), 111-131 (P12) and 141-160 (P15). In order to characterize these epitopes in more detail, CD4(+) T cell clones and cell lines were generated using HBcAg. Surprisingly, 11 of 12 T cell clones examined recognized P15; one recognized P10 (aa 91-111). Of four T cell lines, two recognized P15 and two recognized P5. By peptide mapping, the minimal epitope of P15 was located to residues (147)TVVRRRGRSP(156).
Cao
Tinghua
T
Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium1.
Desombere
Isabelle
I
Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium1.
Vanlandschoot
Peter
P
Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium1.
Sällberg
Matti
M
Division of Clinical Virology, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden2.
Leroux-Roels
Geert
G
Center for Vaccinology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium1.
D000208:Acute Disease; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D006684:HLA-DR Antigens / Q000378:metabolism*; D059810:HLA-DR Serological Subtypes; D006509:Hepatitis B / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010449:Peptide Mapping
D000939:Epitopes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C097337:HLA-DR13 antigen; D006512:Hepatitis B Core Antigens