Induction of HIV-specific cytotoxic T lymphocytes in vivo with hybrid HIV-1 V3:Ty-virus-like particles.
Induction of HIV-specific cytotoxic T lymphocytes in vivo with hybrid HIV-1 V3:Ty-virus-like particles.
复制标题
使用杂交 HIV-1 V3:Ty 病毒样颗粒在体内诱导 HIV 特异性细胞毒性 T 淋巴细胞。
作者：
Guy T. Layton;S. Harris;Andrew J. H. Gearing;M. Hill;Julie S. Cole;Joanne C. Griffiths;N. Burns;A. Kingsman;Sally E. Adams
在一般情况下，它已被证明很难诱导CTL反应使用简单的蛋白质或肽不诉诸于专门的佐剂。在这项研究中，我们发现携带HIV-1 gp120/160包膜蛋白V3区（V3:Ty- vlp）的混合Ty病毒样颗粒形式的颗粒聚合银在缺乏佐剂或脂质载体的BALB/c小鼠中诱导V3特异性CTL。在体外用V3肽再刺激脾细胞是产生效应CTL的必要条件。体外再刺激阶段不需要细胞活化。V3:Ty-VLP诱导的CTL为CD8+ve、h -2d限制性和HIV-1分离特异性（IIIB或MN）。IIIB V3:Ty-VLP和MN V3:Ty-VLP同时启动IIIB和MN V3特异性CTL。然而，只有IIIB V3特异性CTL被携带IIIB、MN和RF V3环序列的杂交Ty-VLP在同一颗粒上引物，这表明CTL表位之间存在分子内竞争，而不是分子间竞争。在直接比较中，V3:Ty-VLP比rgp120有效得多。Rgp160和40mer IIIB V3肽都不能启动V3特异性CTL。这些数据表明，混合Ty-VLP的颗粒性质有助于进入APC并随后进入MHC I类加工途径，并且它们可能是诱导针对HIV-1和其他细胞内病原体的细胞溶解免疫的有用疫苗载体。
In general, it has proven difficult to induce CTL responses using simple proteins or peptides without resorting to specialized adjuvants. In this study we show that particulate polymeric Ag in the form of hybrid Ty virus-like particles carrying the V3 region of HIV-1 gp120/160 envelope protein (V3:Ty-VLP) induce V3-specific CTL in BALB/c mice in the absence of adjuvant or lipid vehicle. In vitro restimulation of splenocytes with V3 peptide was necessary in order to generate effector CTL. Th cell activation was not required for this in vitro restimulation phase. The CTL induced by the V3:Ty-VLP were CD8+ve, H-2d-restricted, and HIV-1 isolate-specific (IIIB or MN). Co-administration of IIIB V3:Ty-VLP and MN V3:Ty-VLP primed both IIIB and MN V3-specific CTL. However, only IIIB V3-specific CTL were primed by hybrid Ty-VLP carrying IIIB, MN, and RF V3 loop sequences on the same particle indicating that there is intra- but not intermolecular competition between CTL epitopes. In direct comparisons, V3:Ty-VLP were substantially more potent than rgp120. Rgp160 and a 40mer IIIB V3 peptide both failed to prime V3-specific CTL. These data suggest that the particulate nature of hybrid Ty-VLP facilitates uptake into APC with subsequent access to the MHC class I processing pathway and that they may be useful vaccine vehicles for inducing cytolytic immunity against HIV-1 and other intracellular pathogens.
使用脂质体中的可溶性蛋白诱导体内细胞毒性 T 淋巴细胞。
DOI：
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发表时间：
1992
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Reddy,R;Zhou,F;Nair,S;Huang,L;Rouse,BT
通讯作者：
Rouse,BT
对外源抗原特异性的细胞毒性 T 淋巴细胞抑制 I 类和 II 类 MHC 限制性抗原呈递。
DOI：
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发表时间：
1992
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Rock,KL;Rothstein,L;Fleischacker,C;Gamble,S
通讯作者：
Gamble,S
免疫优势：MHC II 类分子之间通过共价连接的 T 细胞表位进行分子间竞争。
DOI：
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发表时间：
1992
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Wang,Y;Smith,JA;Gefter,ML;Perkins,DL
通讯作者：
Perkins,DL