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CD4 T-cell memory responses to viral infections of humans show pronounced immunodominance independent of duration or viral persistence.
Title | CD4 T-cell memory responses to viral infections of humans show pronounced immunodominance independent of duration or viral persistence. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Jing, L, Schiffer, JT, Chong, TM, Bruckner, JJ, Davies, HD, Felgner, PL, Haas, J, Wald, A, Verjans, GMGM, Koelle, DM |
Journal | J Virol |
Volume | 87 |
Issue | 5 |
Pagination | 2617-27 |
Date Published | 2013 Mar |
ISSN | 1098-5514 |
Keywords | Antigens, CD137, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cells, Cultured, Herpes Simplex, Herpesvirus 1, Human, Humans, Immunity, Cellular, Immunologic Memory, Interferon-gamma, Interleukin-2, Smallpox Vaccine, Tumor Necrosis Factor-alpha, Vaccines, Attenuated, Vaccinia virus |
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. |
DOI | 10.1128/JVI.03047-12 |
Alternate Journal | J. Virol. |
PubMed ID | 23255792 |