Human CD8+ cytotoxic T cell responses to adenovirus capsid proteins.
Adenoviruses (Ads) cause fatal disease in allogeneic stem cell transplant recipients, but there is no established therapy. Ad-specific CD8+ T cells were detected in PBMC from healthy adults at a mean frequency of 77 per 10(5) CD8+ T cells (range 8-260) by interferon-gamma ELISPOT and cytokine flow cytometry assays. CD8+ T cell lines from 7 of 7 donors exhibited MHC-class-I-restricted killing of targets expressing the capsid protein hexon. In contrast, cytotoxicity against the capsid proteins fiber and penton base was weaker or not detected. Two HLA-A2-restricted hexon epitopes and one HLA-B-restricted epitope were identified, all of which are adjacent to or overlap an HLA-DP4-restricted epitope in the highly conserved C-terminus. Thus, hexon is the immunodominant T cell target among capsid proteins and contains multiple C-terminal epitopes conserved among serotypes. These data support evaluation of donor lymphocyte infusions for treatment of Ad disease post-transplant.
Tang
Jie
J
Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Olive
Melanie
M
Pulmanausahakul
Rojjanaporn
R
Schnell
Matthias
M
Flomenberg
Neal
N
Eisenlohr
Laurence
L
Flomenberg
Phyllis
P
D000256:Adenoviridae / Q000276:immunology* / Q000472:pathogenicity*; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology*; D017931:DNA Primers; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology*
D036022:Capsid Proteins; D017931:DNA Primers; D015395:Histocompatibility Antigens Class I