title: CD4 T-cell memory responses to viral infections of humans show pronounced immunodominance independent of duration or viral persistence.
abstract: 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.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Lichen
authors.initials: L
authors.lastname: Jing
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Schiffer
authors.forename: Tiana M
authors.initials: TM
authors.lastname: Chong
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Bruckner
authors.forename: D Huw
authors.initials: DH
authors.lastname: Davies
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Felgner
authors.forename: Juergen
authors.initials: J
authors.lastname: Haas
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: G M G M
authors.initials: GM
authors.lastname: Verjans
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D012900:Smallpox Vaccine / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014613:Vaccines, Attenuated; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: C078786:DryVax vaccine; D007376:Interleukin-2; D012900:Smallpox Vaccine; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D007371:Interferon-gamma