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Anthony Nesburn, Ruchi Srivastava, Lbachir BenMohamed; Human Asymptomatic Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP13/14 (UL47) Preferentially Recall Polyfunctional Effector Memory CD44highCD62LlowCD8+ TEM Cells and Protect “Humanized” HLA-A*02:01 Transgenic Mice Against Ocular Herpes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3630.
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© ARVO (1962-2015); The Authors (2016-present)
Herpes simplex virus type 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen (Ag) targeted by CD8+ T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8+ T cells play a role in the “natural” protection seen in asymptomatic (ASYMP) individuals (who never had a clinical herpetic disease) has not been elucidated.
Using predictive computer-assisted algorithms, we identify 10 potential HLA-A*02:01-restricted CD8+ T cell epitopes from the 693 amino acids sequence of VP13/14 protein.
Three out of ten epitopes exhibited high to moderate binding affinity to soluble HLA-A*02:01 molecules. The phenotype and function of effector CD8+ T cells specific for each epitope were compared in HLA-A*0201 positive ASYMP vs. SYMP individuals (who have frequent clinical herpetic diseases), using a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107a/b cytotoxic degranulation, and IFN-g production. Higher frequency of multi-functional effector CD8+ T cells directed against three epitopes, VP13/14286-294, VP13/14504-512 and VP13/14544-552, was predominantly detected in ten ASYMP compared to ten SYMP individuals. The three epitopes also predominantly recalled more CD45RAlowCD44highCCR7lowCD62LlowCD8+ effector memory T cells (TEM) in ASYMP individuals. Moreover, immunization of HLA-A*02:01 transgenic mice with the three “ASYMP” CD8+ TEM cell epitopes induced robust and polyfunctional HSV-specific CD8+ TEM cells associated with a strong protective immunity against ocular herpes infection and disease.
Our findings outlining phenotypic and functional features of protective HSV-1 VP13/14-specific CD8+ T cells should guide development of a safe and effective T-cell-based herpes vaccine.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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