Allen T M, Sidney J, del Guercio M F, Glickman R L, Lensmeyer G L, Wiebe D A, DeMars R, Pauza C D, Johnson R P, Sette A, Watkins D I
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison 53715, USA.
J Immunol. 1998 Jun 15;160(12):6062-71.
The majority of immunogenic CTL epitopes bind to MHC class I molecules with high affinity. However, peptides longer or shorter than the optimal epitope rarely bind with high affinity. Therefore, identification of optimal CTL epitopes from pathogens may ultimately be critical for inducing strong CTL responses and developing epitope-based vaccines. The SIV-infected rhesus macaque is an excellent animal model for HIV infection of humans. Although a number of CTL epitopes have been mapped in SIV-infected rhesus macaques, the optimal epitopes have not been well defined, and their anchor residues are unknown. We have now defined the optimal SIV gag CTL epitope restricted by the rhesus MHC class I molecule Mamu-A01 and defined a general peptide binding motif for this molecule that is characterized by a dominant position 3 anchor (proline). We used peptide elution and sequencing, peptide binding assays, and bulk and clonal CTL assays to demonstrate that the optimal Mamu-A01-restricted SIV gag CTL epitope was CTPYDINQM(181-189). Mamu-A01 is unique in that it is found at a high frequency in rhesus macaques, and all SIV-infected Mamu-A01-positive rhesus macaques studied to date develop an immunodominant gag-specific CTL response restricted by this molecule. Identification of the optimal SIV gag CTL epitope will be critical for a variety of studies designed to induce CD8+ CTL responses specific for SIV in the rhesus macaque.
大多数具有免疫原性的细胞毒性T淋巴细胞（CTL）表位与主要组织相容性复合体（MHC）I类分子具有高亲和力结合。然而，比最佳表位更长或更短的肽很少以高亲和力结合。因此，从病原体中鉴定最佳CTL表位可能最终对于诱导强烈的CTL反应和开发基于表位的疫苗至关重要。感染猴免疫缺陷病毒（SIV）的恒河猴是人类感染HIV的优秀动物模型。尽管在感染SIV的恒河猴中已经定位了许多CTL表位，但最佳表位尚未得到很好的定义，其锚定残基也未知。我们现在已经确定了受恒河猴MHC I类分子Mamu-A01限制的最佳SIV gag CTL表位，并确定了该分子的一般肽结合基序，其特征是在第3位有一个占主导地位的锚定残基（脯氨酸）。我们使用肽洗脱和测序、肽结合试验以及大量和克隆CTL试验来证明最佳的受Mamu-A01限制的SIV gag CTL表位是CTPYDINQM(181-189)。Mamu-A01的独特之处在于它在恒河猴中高频出现，并且迄今为止研究的所有感染SIV的Mamu-A01阳性恒河猴都产生了受该分子限制的免疫显性gag特异性CTL反应。鉴定最佳SIV gag CTL表位对于旨在在恒河猴中诱导针对SIV的特异性CD8+ CTL反应的各种研究至关重要。
