Extensive CD4 and CD8 T Cell cross-reactivity between alphaherpesviruses

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Lichen Jing
  • Kerry J. Laing
  • Lichun Dong
  • Ronnie M. Russell
  • Russell S. Barlow
  • Juergen G. Haas
  • Meena S. Ramchandani
  • Christine Johnston
  • Buus, Søren
  • Alec J. Redwood
  • Katie D. White
  • Simon A. Mallal
  • Elizabeth J. Phillips
  • Christine M. Posavad
  • Anna Wald
  • David M. Koelle

The Alphaherpesvirinae subfamily includes HSV types 1 and 2 and the sequence-divergent pathogen varicella zoster virus (VZV). T cells, controlled by TCR and HLA molecules that tolerate limited epitope amino acid variation, might cross-react between these microbes. We show that memory PBMC expansion with either HSV or VZV enriches for CD4 T cell lines that recognize the other agent at the whole-virus, protein, and peptide levels, consistent with bidirectional cross-reactivity. HSV-specific CD4 T cells recovered from HSV-seronegative persons can be explained, in part, by such VZV cross-reactivity. HSV-1-reactive CD8 T cells also cross-react with VZV-infected cells, full-length VZV proteins, and VZV peptides, as well as kill VZV-infected dermal fibroblasts. Mono- and cross-reactive CD8 T cells use distinct TCRB CDR3 sequences. Cross-reactivity to VZV is reconstituted by cloning and expressing TCRA/TCRB receptors from T cells that are initially isolated using HSV reagents. Overall, we define 13 novel CD4 and CD8 HSV-VZV cross-reactive epitopes and strongly imply additional cross-reactive peptide sets. Viral proteins can harbor both CD4 and CD8 HSV/VZV cross-reactive epitopes. Quantitative estimates of HSV/VZV cross-reactivity for both CD4 and CD8 T cells vary from 10 to 50%. Based on these findings, we hypothesize that host herpesvirus immune history may influence the pathogenesis and clinical outcome of subsequent infections or vaccinations for related pathogens and that cross-reactive epitopes and TCRs may be useful for multi-alphaherpesvirus vaccine design and adoptive cellular therapy.

TidsskriftJournal of Immunology
Udgave nummer5
Sider (fra-til)2205-2218
Antal sider14
StatusUdgivet - 2016

ID: 179088361