Extensive CD4 and CD8 T Cell cross-reactivity between alphaherpesviruses

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

doi:10.4049/jimmunol.1502366

Extensive CD4 and CD8 T Cell cross-reactivity between alphaherpesviruses

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

^*Corresponding author for this work

29 Citations (Scopus)

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.

Original language	English
Journal	Journal of Immunology
Volume	196
Issue number	5
Pages (from-to)	2205-2218
Number of pages	14
ISSN	0022-1767
DOIs	https://doi.org/10.4049/jimmunol.1502366
Publication status	Published - 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.4049/jimmunol.1502366

2205.full.pdfFinal published version, 3.76 MB

Cite this

Jing, L., Laing, K. J., Dong, L., Russell, R. M., Barlow, R. S., Haas, J. G., Ramchandani, M. S., Johnston, C., Buus, S., Redwood, A. J., White, K. D., Mallal, S. A., Phillips, E. J., Posavad, C. M., Wald, A., & Koelle, D. M. (2016). Extensive CD4 and CD8 T Cell cross-reactivity between alphaherpesviruses. Journal of Immunology, 196(5), 2205-2218. https://doi.org/10.4049/jimmunol.1502366

@article{f6bec74e534c4fca9f51b212f7d485e7,

title = "Extensive CD4 and CD8 T Cell cross-reactivity between alphaherpesviruses",

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.",

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

year = "2016",

doi = "10.4049/jimmunol.1502366",

language = "English",

volume = "196",

pages = "2205--2218",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "5",

}

TY - JOUR

T1 - Extensive CD4 and CD8 T Cell cross-reactivity between alphaherpesviruses

AU - Jing, Lichen

AU - Laing, Kerry J.

AU - Dong, Lichun

AU - Russell, Ronnie M.

AU - Barlow, Russell S.

AU - Haas, Juergen G.

AU - Ramchandani, Meena S.

AU - Johnston, Christine

AU - Buus, Soren

AU - Redwood, Alec J.

AU - White, Katie D.

AU - Mallal, Simon A.

AU - Phillips, Elizabeth J.

AU - Posavad, Christine M.

AU - Wald, Anna

AU - Koelle, David M.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.4049/jimmunol.1502366

DO - 10.4049/jimmunol.1502366

M3 - Journal article

C2 - 26810224

AN - SCOPUS:84962031561

SN - 0022-1767

VL - 196

SP - 2205

EP - 2218

JO - Journal of Immunology

JF - Journal of Immunology

IS - 5

ER -

Extensive CD4 and CD8 T Cell cross-reactivity between alphaherpesviruses

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this