Journal article
Extensive CD4 and CD8 T Cell Cross-Reactivity between Alphaherpesviruses
The Journal of Immunology, Vol.196(5), pp.2205-2218
2016
Abstract
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.
Details
- Title
- Extensive CD4 and CD8 T Cell Cross-Reactivity between Alphaherpesviruses
- Authors/Creators
- L. Jing (Author/Creator)K.J. Laing (Author/Creator)L. Dong (Author/Creator)R.M. Russell (Author/Creator)R.S. Barlow (Author/Creator)J.G. Haas (Author/Creator)M.S. Ramchandani (Author/Creator)C. Johnston (Author/Creator)S. Buus (Author/Creator)A.J. Redwood (Author/Creator)K.D. White (Author/Creator)S.A. Mallal (Author/Creator)E.J. Phillips (Author/Creator)C.M. Posavad (Author/Creator)A. Wald (Author/Creator)D.M. Koelle (Author/Creator)
- Publication Details
- The Journal of Immunology, Vol.196(5), pp.2205-2218
- Publisher
- American Association of Immunologists
- Identifiers
- 991005540613207891
- Copyright
- © 2016 by The American Association of Immunologists
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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