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Open reading frame 63 of varicella-zoster Virus (VZV) encodes an immediate early (IE) phosphoprotein (IE63) that is believed to be important for viral infectivity and establishing latency. Evidence suggests that VZV-specific T cells are crucial in the control of viral replication; however, data addressing the existence of IE63 protein-specific CD4+ T cells are limited. Using IFN-gamma immunosorbent assays, we identified high frequencies of responses to overlapping peptides spanning the IE63 protein both ex vivo and after in vitro restimulation in healthy VZV-seropositive individuals. We identified a commonly recognised epitope, restricted by HLA-DRB1*1501, which was naturally processed and presented by keratinocytes. We proceeded to investigate the frequency and phenotype of the epitope-specific CD4+ T cells using HLA class II tetrameric complexes. Epitope-specific CD4+ T cells were detectable ex vivo and showed a mixed central and effector-memory differentiation phenotype, with a significant proportion showing evidence of recent activation and rapid effector function. In summary these data implicate persistent low-level or recurrent VZV antigen exposure in healthy immune donors and are compatible with a role for IE63-specific CD4+ T cells in the control of viral reactivation.

Original publication




Journal article


Eur J Immunol

Publication Date





3393 - 3403


Adult, Amino Acid Sequence, Antigen Presentation, Antigens, Viral, CD4-Positive T-Lymphocytes, Cells, Cultured, Epitopes, Female, HLA-DR Antigens, HLA-DRB1 Chains, Herpesvirus 3, Human, Humans, Immediate-Early Proteins, Immunologic Memory, Immunophenotyping, Keratinocytes, Male, Molecular Sequence Data, Peptide Fragments, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets, Viral Envelope Proteins, Virus Activation