Letvin N L, Miller M D, Shen L, Chen Z W, Yasutomi Y
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772.
Semin Immunol. 1993 Jun;5(3):215-23. doi: 10.1006/smim.1993.1025.
An effective HIV vaccine should be capable of eliciting virus-specific cytotoxic T lymphocytes (CTL). We have characterized the cellular and molecular features of a simian immunodeficiency virus of macaques (SIVmac) gag-specific CTL response in rhesus monkeys. We have shown that SIVmac-infected rhesus monkeys expressing the major histocompatibility complex (MHC) class I molecule Mamu-A01 develop a SIVmac gag-specific CTL response which recognizes a 9 amino acid fragment of the gag protein in association with Mamu-A01. Moreover, this peptide/MHC class I recognition is mediated by T cell receptors (TCR) employing a predominant V beta gene family and J beta gene. Using this understanding of a SIVmac-specific CTL response, we have shown that SIVmac-specific CTL can be elicited through three novel approaches to vaccination: a recombinant viral vector, a recombinant bacterial vector and a peptide vaccine. These studies illustrate the utility of the SIV/macaque model in AIDS vaccine research.
一种有效的HIV疫苗应能够引发病毒特异性细胞毒性T淋巴细胞(CTL)。我们已经对恒河猴体内猕猴免疫缺陷病毒(SIVmac)gag特异性CTL反应的细胞和分子特征进行了表征。我们已经表明,感染SIVmac的恒河猴表达主要组织相容性复合体(MHC)I类分子Mamu-A01后,会产生一种SIVmac gag特异性CTL反应,该反应识别与Mamu-A01相关的gag蛋白的一个9氨基酸片段。此外,这种肽/MHC I类识别是由采用主要Vβ基因家族和Jβ基因的T细胞受体(TCR)介导的。基于对SIVmac特异性CTL反应的这种理解,我们已经表明,可以通过三种新型疫苗接种方法引发SIVmac特异性CTL:重组病毒载体、重组细菌载体和肽疫苗。这些研究说明了SIV/猕猴模型在艾滋病疫苗研究中的实用性。