Elsevier

Virology

Volume 412, Issue 2, 10 April 2011, Pages 256-268
Virology

Impaired memory CD8 T cell responses against an immunodominant retroviral cryptic epitope

https://doi.org/10.1016/j.virol.2010.11.013Get rights and content
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Abstract

The immunodominant cryptic epitope SYNTGRFPPL, encoded within open reading frame 2 of the LP-BM5 retroviral gag gene, is critical for protection against retroviral-induced pathogenesis. The goal of this study was to dissect the memory response against this unique immunodominant cryptic epitope. Unlike the protective acute effector population of SYNTGRFPPL-specific CD8 T cells, long-lived SYNTGRFPPL-specific CD8 T cells lacked the ability to protect susceptible mice infected with LP-BM5 retrovirus. Compared to memory CD8 T cells against a conventional epitope with similar MHC-I specificity, primed and restimulated using similar conditions, long-lived SYNTGRFPPL-specific CD8 T cells were impaired in their ability to recall against antigen, with reduced cytolytic capabilities and cytokine production. Since similar priming and restimulation regimes were utilized to generate each effector CD8 T cell population, this study has potentially broad implications with regard to the selection criteria of potent, highly conserved cryptic epitopes for use in epitope-based vaccines.

Keywords

LP-BM5 murine retrovirus
Acute effector CD8 T cell response
Protective memory CD8 T cell response
Central memory
Effector memory
Alternative reading frame
Cryptic epitopes

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1

Present address: Department of Immunology, Wistar Institute, Philadelphia, PA, USA.