Rhesus macaque MHC class I molecules present HLA-B-like peptides
Rhesus macaque MHC class I molecules present HLA-B-like peptides
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DOI：
10.4049/jimmunol.175.1.367
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发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Hildebrand, WH
中科院分区：
文献类型：
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作者：
Hickman-Miller, HD;Bardet, W;Hildebrand, WH
感染 SIV 的印度恒河猴（Macaca mulatta）是人类感染 HIV 的重要动物模型。了解猕猴（M. mulatta I 类（Mamu））MHC I 类肽结合有助于比较 SIV 和 HIV 特异性细胞免疫反应。在本研究中，我们表征了三种 Mamu-A（A*02、A*08、A*11）和三种 Mamu-B（B*01、B*03、B*12）I 类分子的内源肽结合特性。基序比较显示，六种猕猴 I 类分子中的五种（A*02、A*08、A*11、B*01 和 B*03）具有与人类 I 类分子相似的肽结合基序。我们通过串联质谱法对 65 种猕猴内源性肽配体进行测序，其中 5 种是之前从 HLA I 类分子中洗脱下来的。单个配体中九聚体占主导地位，基序和单个配体均表示 P2、P9 和各种辅助锚。有趣的是，Mamu-A 和 Mamu-B 分子的肽结合表现出跨物种肽呈递重叠，主要与 HLA-B 分子重叠。事实上，所有猕猴 I 类分子在肽呈递过程中都呈现 HLA-B 样。值得注意的是，尽管 I 类肽结合沟不同，但猕猴和 HLA 肽呈递还是发生了重叠。猕猴和人类 I 类在 alpha-1 和 alpha-2 结构域内差异高达 42 个氨基酸 (13-23%)，包括特异性口袋 A-F 内的显着差异，结合相同的内源肽。因此，内源肽表征表明猕猴 I 类分子可能是 HLA-B 分子的功能等同物。
SIV-infected Indian rhesus macaques (Macaca mulatta) are an important animal model for humans infected with HIV. Understanding macaque (M. mulatta class I (Mamu)) MHC class I-peptide binding facilitates the comparison of SIV- and HIV-specific cellular immune responses. in this study, we characterized the endogenous peptide-binding properties of three Mamu-A (A*02, A*08, A*11) and three Mamu-B (B*01, B*03, B*12) class I molecules. Motif comparisons revealed that five of the six macaque class I molecules (A*02, A*08, A*11, B*01, and B*03) have peptide-binding motifs similar to those of human class I molecules. Of the 65 macaque endogenous peptide ligands that we sequenced by tandem mass spectroscopy, 5 were previously eluted from HLA class I molecules. Nonamers predominated among the individual ligands, and both the motifs and the individual ligands indicated P2, P9, and various ancillary anchors. Interestingly, peptide binding of the Mamu-A and Mamu-B molecules exhibited cross-species peptide-presentation overlap primarily with HLA-B molecules. Indeed, all of the macaque class I molecules appeared HLA-B-like in peptide presentation. Remarkably, the overlap in macaque- and HLA-peptide presentation occurred despite divergent class I peptide-binding grooves. Macaque and human class I differing by up to 42 aa (13-23%) within the alpha-1 and alpha-2 domains, including substantial divergence within specificity pockets A-F, bound the same endogenous peptide. Therefore, endogenous peptide characterization indicates that macaque class I molecules may be the functional equivalents of HLA-B molecules.