Evidence as a HIV-1 self-defense vaccine of cyclic chimeric dodecapeptide warped from undecapeptidyl arch of extracellular loop 2 in both CCR5 and CXCR4.
Evidence as a HIV-1 self-defense vaccine of cyclic chimeric dodecapeptide warped from undecapeptidyl arch of extracellular loop 2 in both CCR5 and CXCR4.
复制标题
作为 HIV-1 自卫疫苗的证据，环状嵌合十二肽从 CCR5 和 CXCR4 中细胞外环 2 的十一肽基拱弯曲。
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
S. Shoji
中科院分区：
文献类型：
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作者：
S. Misumi;N. Takamune;Y. Ido;S. Hayashi;M. Endo;R. Mukai;K. Tachibana;M. Umeda;S. Shoji
在趋化因子受体（CCR5和CXCR4）细胞外环2 （ECL2）非肽基弓(UPA：在CCR5中从R（168）到C（178)，在CXCR4中从N（176）到C(186)）中，由间隔臂Gly-Asp二肽和CCR5的S(169)-Q(170)-K(171)-E(172)-G（173）和E(179)-A(180)-D(181)-D（182)-R(183)）组成的环状嵌合十二肽基多抗原肽（cCD-MAP）构建了新的构象特异性抗体。在提出的抗体中，一种单克隆抗体CPMAb-I （IgMkappa）与cCD-MAP反应，但不与线性嵌合十二肽- map反应。抗体分别与表达CCR5或CXCR4的细胞反应，而不与不表达这些共受体的细胞反应。此外，在使用表达ccr5的Hela/CD4（+）细胞克隆1-10 （MAGIC-5）进行的HIV-1药物敏感性的新表型试验中，该抗体以剂量依赖的方式显著抑制X4、R5或R5X4病毒的感染。此外，cpmab -1干扰与产生cpmab -1的杂种瘤共培养的Molt4#8细胞的LAV-1（BRU）感染（m.o i = 0.01），且对基质细胞衍生因子1 α (sdf -1 α)诱导的趋化性和钙内流均无显著干扰。因此，针对cCD-MAP产生的抗体对HIV-1感染提供了强大的保护或防御。因此，我们提出cCD-MAP或其衍生免疫原作为基于HIV-1辅受体的自卫疫苗的新候选。
Novel conformation-specific antibodies were raised against a cyclic chimeric dodecapeptidyl multiple antigen peptide (cCD-MAP) constructed with a spacer-armed Gly-Asp dipeptide and two pentapeptides (S(169)-Q(170)-K(171)-E(172)-G(173) of CCR5 and E(179)-A(180)-D(181)-D(182)-R(183) of CXCR4) which are components of the undecapeptidyl arch (UPA: from R(168) to C(178) in CCR5, from N(176) to C(186) in CXCR4) of extracellular loop 2 (ECL2) in chemokine receptors (CCR5 and CXCR4). Of the antibodies raised, one monoclonal antibody, CPMAb-I (IgMkappa), reacted with cCD-MAP, but not with the linear chimeric dodecapeptide-MAP. The antibody reacted with the cells separately expressing CCR5 or CXCR4, but not with those not expressing the coreceptors. Moreover, the antibody markedly suppressed infection by X4, R5, or R5X4 virus in a dose-dependent manner in a new phenotypic assay for drug susceptibility of HIV-1 using CCR5-expressing Hela/CD4(+) cell clone 1-10 (MAGIC-5). Moreover, CPMAb-I interfered with LAV-1(BRU) infection (m.o.i. = 0.01) of Molt4#8 cells cocultured with CPMAb-I-producing hybridoma in the transwell, and significantly interfered with neither chemotaxis nor calcium influx induced with stromal cell-derived factor 1 alpha (SDF-1alpha). Thus, the antibody raised against the cCD-MAP provides powerful protection or defense against HIV-1 infection. We therefore propose the cCD-MAP or its derivative immunogen as a novel candidate for an HIV-1 coreceptor-based self-defense vaccine.