Phenotypic analysis of human CD4+ T cells specific for immediate-early 63 protein of varicella-zoster virus

Eur J Immunol. 2007 Dec;37(12):3393-403. doi: 10.1002/eji.200737648.


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.

MeSH terms

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


  • Antigens, Viral
  • Epitopes
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*15:01 antigen
  • Immediate-Early Proteins
  • Peptide Fragments
  • Viral Envelope Proteins
  • immediate early protein 63, Human herpesvirus 3