{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:22Z","timestamp":1787030842907,"version":"build-2736575974"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013reactive 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\u2013VZV 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1502366","type":"journal-article","created":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T22:58:09Z","timestamp":1453762689000},"page":"2205-2218","source":"Crossref","is-referenced-by-count":59,"title":["Extensive CD4 and CD8 T Cell Cross-Reactivity between Alphaherpesviruses"],"prefix":"10.1093","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5938-4171","authenticated-orcid":false,"given":"Lichen","family":"Jing","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Washington , Seattle, WA 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98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen G","family":"Haas","sequence":"additional","affiliation":[{"name":"Max von Pettenkofer-Institute , 80336 Munich ,","place":["Germany"]},{"name":"Division of Pathway Medicine, University of Edinburgh , Edinburgh EH16 4SB ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0298-474X","authenticated-orcid":false,"given":"Meena S","family":"Ramchandani","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington , Seattle, WA 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A","family":"Mallal","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases, Murdoch University , Perth, Western Australia 6150 ,","place":["Australia"]},{"name":"Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN 37235"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J","family":"Phillips","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases, Murdoch University , Perth, Western Australia 6150 ,","place":["Australia"]},{"name":"Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN 37235"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M","family":"Posavad","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"},{"name":"Department of Laboratory Medicine, University of Washington , Seattle, WA 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