Miller M D, Yamamoto H, Hughes A L, Watkins D I, Letvin N L
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772.
J Immunol. 1991 Jul 1;147(1):320-9.
Infection of macaque monkeys with the simian immunodeficiency virus of macaques (SIVmac) results in disease similar to human AIDS. Therefore, the macaque monkey is proving to be an important model for testing the effectiveness of various AIDS vaccine approaches. A detailed analysis of the cellular immune responses is necessary for the evaluation of candidate vaccines. However, this has not been possible in macaques, due, in part, to the unknown nature of the MHC molecules that restrict their T lymphocytes. In our report we demonstrate that a particular MHC class I molecule involved in the rhesus monkey's effector T lymphocyte response to SIVmac is expressed at a high frequency in a colony of rhesus monkeys. SIVmac-infected monkeys that express this MHC class I molecule all develop CTL that are restricted by that molecule and recognize an identical nine amino acid epitope of the SIVmac gag protein. This MHC class I molecule has been defined as an HLA-A homolog by cDNA cloning and sequencing. It has also been expressed in an MHC class I-deficient cell line to demonstrate directly the cloned molecule's capacity to bind and present peptide Ag to CTL. These studies illustrate that AIDS virus-specific CTL can be characterized in detail in the rhesus monkey and lay the foundation for exploring novel approaches to AIDS virus vaccination in this species.
猕猴感染猕猴猿免疫缺陷病毒(SIVmac)会引发与人类艾滋病相似的疾病。因此,猕猴正被证明是测试各种艾滋病疫苗方法有效性的重要模型。对细胞免疫反应进行详细分析对于评估候选疫苗是必要的。然而,在猕猴中这一直无法实现,部分原因是限制其T淋巴细胞的MHC分子的性质尚不清楚。在我们的报告中,我们证明了参与恒河猴效应T淋巴细胞对SIVmac反应的一种特定MHC I类分子在一群恒河猴中高频表达。表达这种MHC I类分子的SIVmac感染猕猴均产生受该分子限制并识别SIVmac gag蛋白相同九氨基酸表位的CTL。通过cDNA克隆和测序,这种MHC I类分子已被定义为HLA - A同源物。它也已在MHC I类缺陷细胞系中表达,以直接证明克隆分子结合并向CTL呈递肽抗原的能力。这些研究表明,在恒河猴中可以详细表征艾滋病病毒特异性CTL,并为探索该物种艾滋病病毒疫苗接种的新方法奠定基础。