HLA-A2-restricted human CD8(+) cytotoxic T lymphocyte responses to a novel epitope in vaccinia virus that is conserved among orthopox viruses.
Classical major histocompatibility complex class I-restricted CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in protective immunity against infection with smallpox virus. The identification of target antigens is crucial for defining the role played by CD8(+) CTL responses in host resistance to smallpox and for the design of vaccines that produce effective cell-based responses. We report the identification of a novel human leukocyte antigen-A*0201-restricted epitope (J8R(11-19)) within A55R of vaccinia virus (VV) that is conserved in J8R of smallpox virus variola major. The J8R(11-19)-specific CTL line and CTL clone exerted physiologically relevant functions as they recognized VV-infected lymphoblastoid JY cells or autologous B lymphoblastoid cell lines, and the cytolytic activity was accompanied by the production of interferon- gamma , tumor necrosis factor- alpha , and interleukin-2. The CTL response was detected in individuals who had been vaccinated >30 years ago or had recently received a booster of current smallpox vaccine (Dryvax) but not in VV-naive donors.
Dong
Yuzhi
Y
Center for Laboratory Investigation, Department of Pathology, Laboratory Medicine, and Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, Newark, NJ 07103, USA.
Denny
Thomas N
TN
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D017124:Conserved Sequence / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D012900:Smallpox Vaccine / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014616:Vaccinia virus / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D007376:Interleukin-2; D012900:Smallpox Vaccine; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D007371:Interferon-gamma