Characterization of the peptide binding motif of a rhesus MHC class I molecule (Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency virus.
Characterization of the peptide binding motif of a rhesus MHC class I molecule (Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency virus.
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DOI：
10.4049/jimmunol.160.12.6062
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发表时间：
1998-06
影响因子：
4.4
通讯作者：
Todd M. Allen;J. Sidney;M. del Guercio;R. Glickman;G. Lensmeyer;D. Wiebe;R. Demars;C. Pauza;R. Johnson;A. Sette;D. Watkins
中科院分区：
文献类型：
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作者：
Todd M. Allen;J. Sidney;M. del Guercio;R. Glickman;G. Lensmeyer;D. Wiebe;R. Demars;C. Pauza;R. Johnson;A. Sette;D. Watkins
大多数免疫原性CTL表位与MHC-I类分子具有高亲和力。然而，比最佳表位更长或更短的多肽很少与高亲和力结合。因此，从病原体中识别最佳的CTL表位可能最终对诱导强大的CTL反应和开发基于表位的疫苗至关重要。感染SIV的恒河猴是人类感染HIV的良好动物模型。虽然已经在SIV感染的恒河猴中定位了一些CTL表位，但最佳表位还没有很好地定义，其锚定残基也是未知的。我们现在已经定义了由恒河猴MHC I类分子MAMU-A*01限制的最佳SIV Gag CTL表位，并为该分子定义了一个以优势地位3锚(Pro)为特征的通用多肽结合基序。我们通过多肽洗脱和测序、多肽结合试验、原代和克隆性CTL试验证明了MAMU-A*01限制性SIV Gag CTL表位为CTPYDINQM(181-189)。MAMU-A*01是独一无二的，因为它在恒河猴中发现的频率很高，到目前为止研究的所有SIV感染的MAMU-A*01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。确定最佳的SIV Gag CTL表位对于各种旨在诱导恒河猴SIV特异性CD8+CTL反应的研究将是至关重要的。
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-A*01 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-A*01-restricted SIV gag CTL epitope was CTPYDINQM(181-189). Mamu-A*01 is unique in that it is found at a high frequency in rhesus macaques, and all SIV-infected Mamu-A*01-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.