Hoof Ilka, Keşmir Can, Lund Ole, Nielsen Morten
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
AIDS. 2008 Jul 11;22(11):1299-303. doi: 10.1097/QAD.0b013e328302f39f.
Major histocompatibility complex (MHC) class I molecules allow immune surveillance by presenting a snapshot of the intracellular state of a cell to circulating cytotoxic T lymphocytes. The MHC class I alleles of an HIV-1 infected individual strongly influence the level of viremia and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors.
To investigate if long-term non-progressors and chimpanzees have functional similarities in their MHC class I repertoire.
We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee.
We demonstrate that human MHC with control of HIV-1 viral load share binding motifs with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control.
主要组织相容性复合体(MHC)I类分子通过向循环中的细胞毒性T淋巴细胞呈现细胞内状态的快照来实现免疫监视。HIV-1感染者的MHC I类等位基因强烈影响病毒血症水平和向艾滋病的进展速度。黑猩猩能够控制HIV-1病毒复制并发展为慢性感染,但不会进展为艾滋病。在人类长期非进展者中也观察到类似的病程。
研究长期非进展者和黑猩猩在其MHC I类库中是否具有功能相似性。
我们比较了与HIV-1感染者不同病毒血症水平相关的人类MHC分子组与黑猩猩MHC分子组的特异性。
我们证明,控制HIV-1病毒载量的人类MHC与黑猩猩MHC具有共同的结合基序。此外,我们发现,与高病毒载量相关的人类MHC相比,与低病毒载量相关的黑猩猩和人类MHC预计会引发更广泛的Gag特异性免疫反应,从而支持了早期的研究结果,即Gag特异性免疫反应对于HIV-1的控制至关重要。