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

L Jones, AP Black, GN Malavige… - European journal of …, 2007 - Wiley Online Library
European journal of immunology, 2007Wiley Online Library
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‐γ immunosorbent assays, we identified high frequencies of responses
to overlapping peptides spanning the IE63 protein both ex vivo and after in vitro …
Abstract
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‐γ 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.
Wiley Online Library