Reche Pedro A, Keskin Derin B, Hussey Rebecca E, Ancuta Petronela, Gabuzda Dana, Reinherz Ellis L
Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Harvard Medical School, Boston, MA 02115, USA.
Med Immunol. 2006 May 18;5:1. doi: 10.1186/1476-9433-5-1.
Cytotoxic T lymphocytes (CTL) protect against viruses including HIV-1. To avoid viral escape mutants that thwart immunity, we chose 25 CTL epitopes defined in the context of natural infection with functional and/or structural constraints that maintain sequence conservation. By combining HLA binding predictions with knowledge concerning HLA allele frequencies, a metric estimating population protection coverage (PPC) was computed and epitope pools assembled. Strikingly, only a minority of immunocompetent HIV-1 infected individuals responds to pools with PPC >95%. In contrast, virus-naive individuals uniformly expand IFNgamma producing cells and mount anti-HIV-1 cytolytic activity. This disparity suggests a vaccine design paradigm shift from infected to normal subjects.
细胞毒性T淋巴细胞（CTL）可抵御包括HIV-1在内的病毒。为避免出现阻碍免疫的病毒逃逸突变体，我们选择了25个在自然感染背景下定义的CTL表位，这些表位具有维持序列保守性的功能和/或结构限制。通过将HLA结合预测与关于HLA等位基因频率的知识相结合，计算了一个估计群体保护覆盖率（PPC）的指标，并组装了表位库。令人惊讶的是，只有少数具有免疫活性的HIV-1感染个体对PPC>95%的表位库有反应。相比之下，未感染病毒的个体均能使产生IFNγ的细胞扩增并产生抗HIV-1细胞溶解活性。这种差异表明疫苗设计模式从感染个体转向了正常个体。
