Department of Microbiology and Immunology and Norris Cotton Cancer Center, Dartmouth Medical School, One Medical Center Drive, Borwell Bldg, Lebanon, NH 03756, USA.
Virology. 2011 Apr 10;412(2):256-68. doi: 10.1016/j.virol.2010.11.013. Epub 2011 Feb 4.
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.
免疫显性隐蔽表位 SYNTGRFPPL 编码在 LP-BM5 逆转录病毒 gag 基因的开放阅读框 2 内，对于抵抗逆转录病毒诱导的发病机制至关重要。本研究的目的是剖析针对这种独特免疫显性隐蔽表位的记忆反应。与针对 SYNTGRFPPL 特异性 CD8 T 细胞的保护性急性效应细胞群不同，长寿的 SYNTGRFPPL 特异性 CD8 T 细胞缺乏保护易感小鼠免受 LP-BM5 逆转录病毒感染的能力。与具有相似 MHC-I 特异性的常规表位相比，用相似的条件进行初始和再刺激，长寿的 SYNTGRFPPL 特异性 CD8 T 细胞在其针对抗原的召回能力上受损，细胞溶解能力和细胞因子产生减少。由于每个效应 CD8 T 细胞群体都使用相似的初始和再刺激方案进行生成，因此这项研究对于选择用于基于表位疫苗的有效、高度保守的隐蔽表位的选择标准具有广泛的意义。
