CD4 T-Cell memory responses to viral infections of humans show pronounced immunodominance independent of duration or viral persistence
Journal of Virology , Volume 87 - Issue 5 p. 2617- 2627
Little is known concerning immunodominance within the CD4 T-cell response to viral infections and its persistence into longterm 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.
|Journal of Virology|
|Organisation||Department of Virology|
Jing, L, Schiffer, A.A, Chong, T.M, Bruckner, J.J, Davies, D.H, Felgner, P.L, … Koellea, D.M. (2013). CD4 T-Cell memory responses to viral infections of humans show pronounced immunodominance independent of duration or viral persistence. Journal of Virology, 87(5), 2617–2627. doi:10.1128/JVI.03047-12