A synthetic peptide from the first conserved region in the envelope protein gp160 is a strong T-cell epitope in HIV-infected chimpanzees and humans.

A synthetic peptide from the first conserved region in the envelope protein gp160 is a strong T-cell epitope in HIV-infected chimpanzees and humans.
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来自包膜蛋白 gp160 中第一个保守区域的合成肽是感染 HIV 的黑猩猩和人类中的强 T 细胞表位。

DOI:
10.1089/vim.1998.11.147
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发表时间:
1998
期刊:
Viral immunology.
影响因子:
--
通讯作者:
Sastry,KJ
Sastry,KJ
中科院分区:
--
文献类型:
--
作者:
Nehete,PN;Schapiro,SJ;Johnson,PC;Murthy,KK;Satterfield,WC;Sastry,KJ

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我们早先报道了对应于人类免疫缺陷病毒1型(HIV-1)包膜蛋白gp 160中高度保守区域的合成肽,特别是来自氨基末端第一保守区域的11个氨基酸序列(肽104),能够在几种近交系小鼠品系以及远交系恒河猴中诱导强烈的HIV特异性T细胞增殖反应。我们现在已经获得证据表明,在9只慢性感染HIV-1的黑猩猩中有7只(p≤ 0.05)和17只HIV+个体中有8只(p≤ 0.001)对肽104存在显著水平的增殖反应。此外,先前在我们的鼠和恒河猴模型系统中鉴定的其他四种保守的HIV病毒衍生肽在感染HIV-1的黑猩猩和人类中被广泛认为是T细胞表位。在受感染的受试者中,没有一个外周血单核细胞显示对无关对照肽的增殖反应。此外,无论是控制正常黑猩猩,也没有HIV-血清阴性的个人表现出增殖反应的保守肽。关于体液应答,没有黑猩猩的血清样品显示与任何保守肽的反应性,并且在17名患者中的3名中仅观察到低水平的针对肽104的抗体应答(p> 0.05)。重要的是,三个保守的HIV衍生肽,包括肽104,与文献中报道的序列重叠,这些序列是无症状HIV+个体中病毒诱导的细胞毒性T淋巴细胞的表位。这些观察结果,连同我们在多种动物模型和人类中的结果,确立了这些保守的HIV病毒衍生肽,特别是肽104,是重要的T细胞表位,具有诱导人类HIV特异性细胞介导的免疫应答的潜在用途。
We reported earlier that synthetic peptides corresponding to highly conserved regions in the envelope protein gp160 of the human immunodeficiency virus type 1 (HIV-1), in particular an 11-amino acid sequence (peptide 104) from the first conserved region at the ammo-terminus, were capable of inducing strong HIV-specific T-cell proliferative responses in several inbred mouse strains as well as in outbred Rhesus monkeys. We have now obtained evidence of the presence of significant levels of proliferative response to peptide 104 in 7 of 9 chimpanzees chronically infected with HIV-1 (p≤ 0.05) and 8 of 17 HIV+individuals (p≤ 0.001). Further, four other conserved HIV envelope-derived peptides, identified previously in our murine and Rhesus monkey model systems, were widely recognized as T-cell epitopes in both chimpanzees and humans infected with HIV-1. In none of the infected subjects did peripheral blood mononuclear cells show proliferative responses to unrelated control peptides. Also, neither the control normal chimpanzees nor HIV-seronegative individuals showed proliferative responses to the conserved peptides. With respect to the humoral responses, serum samples from none of the chimpanzees showed reactivity with any of the conserved peptides, and only low levels of antibody responses against peptide 104 were observed in 3 of the 17 patients (p> 0.05). Importantly, three of the conserved envelope-derived peptides, including peptide 104, overlap with sequences that were reported in the literature to be epitopes for virus-induced cytotoxic T lymphocytes in asymptomatic HIV+individuals. These observations, together with our results in multiple animal models and humans, establish that these conserved HIV envelope-derived peptides, particularly peptide 104, are significant T-cell epitopes with potential usefulness for induction of HIV-specific cell-mediated immune responses in humans.
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影响因子: 4.4
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发表时间: 1988
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期刊: ENDOCRINOLOGY
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