June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
HLA-A02:01-Restricted Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP11/12 Preferentially Recall Polyfunctional Effector Memory CD8+ T Cells from Seropositive Asymptomatic Individuals and Protect “Humanized” HLA-A*02:01 Transgenic Mice Against Ocular Herpes
Author Affiliations & Notes
  • Ruchi Srivastava
    Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University Of California Irvine, Irvine, CA
  • Arif A Khan
    Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University Of California Irvine, Irvine, CA
  • Doran Spencer
    Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University Of California Irvine, Irvine, CA
  • Sumit Garg
    Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University Of California Irvine, Irvine, CA
  • Anthony B Nesburn
    Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University Of California Irvine, Irvine, CA
  • Steven Wechsler
    Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University Of California Irvine, Irvine, CA
  • Lbachir BenMohamed
    Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University Of California Irvine, Irvine, CA
  • Footnotes
    Commercial Relationships Ruchi Srivastava, None; Arif Khan, None; Doran Spencer, None; Sumit Garg, None; Anthony Nesburn, None; Steven Wechsler, None; Lbachir BenMohamed, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1858. doi:
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      Ruchi Srivastava, Arif A Khan, Doran Spencer, Sumit Garg, Anthony B Nesburn, Steven Wechsler, Lbachir BenMohamed; HLA-A02:01-Restricted Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP11/12 Preferentially Recall Polyfunctional Effector Memory CD8+ T Cells from Seropositive Asymptomatic Individuals and Protect “Humanized” HLA-A*02:01 Transgenic Mice Against Ocular Herpes. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1858.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The Herpes Simplex Virus type 1 virion tegument phosphoprotein 11/12 (HSV-1 VP11/12) is a major antigen targeted by CD8+ T cells from HSV-seropositive individuals. However, whether and which VP11/12-epitope-specific CD8+ T cells play a role in the “natural” protection seen in seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined.

Methods: In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8+ T cell epitopes from the 718 amino acids sequence of VP11/12.

Results: Three out of ten epitopes exhibited high to moderate binding affinity to HLA-A*02:01 molecules. In ten sequentially studied HLA-A*02:01 positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust and polyfunctional effector CD8+ T-cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107a/b cytotoxic degranulation, IFN-g and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228 and VP11/12702-710. Interestingly, ASYMP individuals had significantly higher proportion of CD45RAlowCCR7lowCD44highCD62LlowCD27lowCD28lowCD8+ effector memory T cells (TEM) specific to the three epitopes, compared to symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpetic disease). Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8+ T cell epitopes induced robust and polyfunctional epitope-specific CD8+ TEM cells, in both cornea and trigeminal ganglia (TG), that were associated with a strong protective immunity against ocular herpes infection and disease.

Conclusions: Our findings outline phenotypic and functional features of protective HSV-specific CD8+ T cells that should guide the development of an effective T-cell-based herpes vaccine.

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