CD4 T-cell memory responses to viral infections of humans show pronounced immunodominance independent of duration or viral persistence

Lichen Jing, Joshua T Schiffer, Tiana M Chong, Joseph J Bruckner, D Huw Davies, Phillip L Felgner, Juergen Haas, Anna Wald, G M G M Verjans, David M Koelle

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)2617-27
Number of pages11
JournalJournal of Virology
Issue number5
Publication statusPublished - Mar 2013


  • Herpes Simplex
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Humans
  • Herpesvirus 1, Human
  • Antigens, CD137
  • CD4-Positive T-Lymphocytes
  • Vaccines, Attenuated
  • Smallpox Vaccine
  • Vaccinia virus
  • Immunity, Cellular
  • Cells, Cultured
  • Interleukin-2
  • CD8-Positive T-Lymphocytes
  • Immunologic Memory


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