{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T04:23:59Z","timestamp":1771993439256,"version":"3.50.1"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"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":[[2014,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Intraocular varicella-zoster virus (VZV) and HSV type 1 (HSV-1) infections cause sight-threatening uveitis. The disease is characterized by an intraocular inflammatory response involving herpesvirus-specific T cells. T cell reactivity to the noncausative human alphaherpesvirus (\u03b1HHV) is commonly detected in the affected eyes of herpetic uveitis patients, suggesting the role of cross-reactive T cells in the disease. This study aimed to identify and functionally characterize intraocular human alphaherpesvirus cross-reactive T cells. VZV protein immediate early 62 (IE62), which shares extensive homology with HSV ICP4, is a previously identified T cell target in VZV uveitis. Two VZV-specific CD4 T cell clones (TCC), recovered from the eye of a VZV uveitis patient, recognized the same IE62918\u2013927 peptide using different TCR and HLA-DR alleles. The IE62918\u2013927 peptide bound with high affinity to multiple HLA-DR alleles and was recognized by blood-derived T cells of 5 of 17 HSV-1\/VZV-seropositive healthy adults but not in cord blood donors (n = 5). Despite complete conservation of the IE62 epitope in the orthologous protein ICP4 of HSV-1 and HSV-2, the TCC recognized VZV and HSV-1\u2013 but not HSV-2\u2013infected B cells. This was not attributed to proximal epitope-flanking amino acid polymorphisms in HSV-2 ICP4. Notably, VZV\/HSV-1 cross-reactive CD4 T cells controlled VZV but not HSV-1 infection of human primary retinal pigment epithelium (RPE) cells. In conclusion, we report on the first VZV\/HSV-1 cross-reactive CD4 T cell epitope, which is HLA-DR promiscuous and immunoprevalent in coinfected individuals. Moreover, ocular-derived peptide-specific CD4 TCC controlled VZV but not HSV-1 infection of RPE cells, suggesting that HSV-1 actively inhibits CD4 T cell activation by infected human RPE cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1302307","type":"journal-article","created":{"date-parts":[[2014,3,13]],"date-time":"2014-03-13T04:19:30Z","timestamp":1394684370000},"page":"3730-3739","source":"Crossref","is-referenced-by-count":19,"title":["Functional Characterization of Ocular-Derived Human Alphaherpesvirus Cross-Reactive CD4 T Cells"],"prefix":"10.1093","volume":"192","author":[{"given":"Werner J D","family":"Ouwendijk","sequence":"first","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center , 3015 CE Rotterdam,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemieke","family":"Geluk","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Leiden University Medical Center , 2333 ZA Leiden,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saskia L","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center , 3015 CE Rotterdam,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Getu","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center , 3015 CE Rotterdam,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert D M E","family":"Osterhaus","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center , 3015 CE Rotterdam,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georges M G M","family":"Verjans","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus Medical Center , 3015 CE Rotterdam,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,4,15]]},"reference":[{"key":"2025032404241808900_r1","first-page":"2501","volume-title":"Fields Virology","author":"Roizman","year":"2007","edition":"5th"},{"key":"2025032404241808900_r2","first-page":"2773","volume-title":"Fields Virology","author":"Cohen","year":"2007","edition":"5th"},{"key":"2025032404241808900_r3","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/infdis\/154.3.422","article-title":"Early immune response in healthy and immunocompromised subjects with primary varicella-zoster virus infection","volume":"154","author":"Arvin","year":"1986","journal-title":"J. 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