CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Building 3, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China.
J Virol. 2011 Jul;85(14):7372-83. doi: 10.1128/JVI.00350-11. Epub 2011 May 11.
Major histocompatibility complex class I (MHC I)-restricted CD8(+) T-cell responses play a pivotal role in anti-human immunodeficiency virus (HIV) immunity and the control of viremia. The rhesus macaque is an important animal model for HIV-related research. Among the MHC I alleles of the rhesus macaque, Mamu-A 02 is prevalent, presenting in ≥20% of macaques. In this study, we determined the crystal structure of Mamu-A 02, the second structure-determined MHC I from the rhesus macaque after Mamu-A 01. The peptide presentation characteristics of Mamu-A 02 are exhibited in complex structures with two typical Mamu-A 02-restricted CD8(+) T-cell epitopes, YY9 (Nef159 to -167; YTSGPGIRY) and GY9 (Gag71 to -79; GSENLKSLY), derived from simian immunodeficiency virus (SIV). These two peptides utilize similar primary anchor residues (Ser or Thr) at position 2 and Tyr at position 9. However, the central region of YY9 is different from that of GY9, a difference that may correlate with the immunogenic variance of these peptides. Further analysis indicated that the distinct conformations of these two peptides are modulated by four flexible residues in the Mamu-A 02 peptide-binding groove. The rare combination of these four residues in Mamu-A 02 leads to a variant presentation for peptides with different residues in their central regions. Additionally, in the two structures of the Mamu-A 02 complex, we compared the binding of rhesus and human β(2) microglobulin (β(2)m) to Mamu-A 02. We found that the peptide presentation of Mamu-A 02 is not affected by the interspecies interaction with human β(2)m. Our work broadens the understanding of CD8(+) T-cell-specific immunity against SIV in the rhesus macaque.
主要组织相容性复合体 I 类（MHC I）限制的 CD8(+) T 细胞反应在抗人类免疫缺陷病毒（HIV）免疫和控制病毒血症中发挥关键作用。恒河猴是 HIV 相关研究的重要动物模型。在恒河猴的 MHC I 等位基因中，Mamu-A02 较为普遍，在≥20%的猴子中出现。在这项研究中，我们确定了 Mamu-A02 的晶体结构，这是继 Mamu-A01 之后第二种确定结构的恒河猴 MHC I。Mamu-A02 的肽呈递特征在与两种典型的 Mamu-A02 限制性 CD8(+) T 细胞表位的复合物结构中得到展示，YY9（Nef159 至-167；YTSGPGIRY）和 GY9（Gag71 至-79；GSENLKSLY），源自猿猴免疫缺陷病毒（SIV）。这两种肽在位置 2 处使用类似的主要锚定残基（Ser 或 Thr）和位置 9 处的 Tyr。然而，YY9 的中心区域与 GY9 不同，这种差异可能与这些肽的免疫原性差异相关。进一步分析表明，这两种肽的独特构象是由 Mamu-A02 肽结合槽中的四个柔性残基调节的。Mamu-A02 中这四个残基的罕见组合导致其呈现具有不同中心区域残基的肽的不同构象。此外，在 Mamu-A02 的两种结构中，我们比较了恒河猴和人类β(2)微球蛋白（β(2)m）与 Mamu-A02 的结合。我们发现 Mamu-A02 的肽呈递不受与人类β(2)m 的种间相互作用的影响。我们的工作拓宽了对恒河猴中 SIV 特异性 CD8(+) T 细胞免疫的理解。
