期刊
JOURNAL OF VIROLOGY
卷 87, 期 5, 页码 2617-2627出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.03047-12
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资金
- NIH [AI081060, AI30731, AI067496, AI094019, NO1-AI40069, U01AI056464, AI058365, U01AI061363, K23 AI0872606]
- Poxvirus T-Cell Vaccine Discovery Consortium (PTVDC) from the Gates Foundation
- BayGene (Bayerisches Staatsministerium fur Wissenschaft, Forschung und Kunst), DFG [SFB 576, BA 1165/5-1]
- BayGene (Bayerisches Staatsministerium fur Wissenschaft, Forschung und Kunst), MRC [G0501453]
Little is known concerning immunodominance within the CD4 T-cell response to viral infections and its persistence into long-term memory. We tested CD4 T-cell reactivity against each viral protein in persons immunized with vaccinia virus (VV), either recently or more than 40 years ago, as a model self-limited viral infection. Similar tests were done with persons with herpes simplex virus 1 (HSV-1) infection as a model chronic infection. We used an indirect method capable of counting the CD4 T cells in blood reactive with each individual viral protein. Each person had a clear CD4 T-cell dominance hierarchy. The top four open reading frames accounted for about 40% of CD4 virus-specific T cells. Early and long-term memory CD4 T-cell responses to vaccinia virus were mathematically indistinguishable for antigen breadth and immunodominance. Despite the chronic intermittent presence of HSV-1 antigen, the CD4 T-cell dominance and diversity patterns for HSV-1 were identical to those observed for vaccinia virus. The immunodominant CD4 T-cell antigens included both long proteins abundantly present in virions and shorter, nonstructural proteins. Limited epitope level and direct ex vivo data were also consistent with pronounced CD4 T-cell immunodominance. We conclude that human memory CD4 T-cell responses show a pattern of pronounced immunodominance for both chronic and self-limited viral infections and that this pattern can persist over several decades in the absence of antigen.
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