Carboxyl-terminal and central regions of human immunodeficiency virus-1 NEF recognized by cytotoxic T lymphocytes from lymphoid organs. An in vitro limiting dilution analysis.
Carboxyl-terminal and central regions of human immunodeficiency virus-1 NEF recognized by cytotoxic T lymphocytes from lymphoid organs. An in vitro limiting dilution analysis.
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人类免疫缺陷病毒 1 NEF 的羧基末端和中心区域被淋巴器官的细胞毒性 T 淋巴细胞识别。
DOI：
10.1172/jci115585
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发表时间：
1992
期刊：
影响因子：
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通讯作者：
B. Autran
中科院分区：
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作者：
F. Hadida;A. Parrot;M. Kieny;B. Sadat;C. Mayaud;P. Debré;B. Autran
在血清学阳性患者的淋巴器官中分析了对人类免疫缺陷病毒（HIV）蛋白特异的细胞毒性T淋巴细胞（CTL）。事实上，在这些器官中，活跃的HIV复制与主要的CD 8+淋巴细胞浸润共存。我们在先前的报告中已经表明，HIV血清阳性患者的肺部被HIV特异性CD 8+淋巴细胞浸润。在本报告中，我们表明，HIV特异性CTL反应也可以在淋巴结和脾脏中检测到，主要针对ENV，GAG和NEF HIV-1蛋白。通过表位作图进一步表征初级NEF特异性CTL应答。通过有限稀释分析进行表位特异性CTL频率的测定。结果表明，除了NEF的中心区域（AA 66 -148）外，CTL还识别一个新的免疫显性区域。该区域对应于NEF的羧基末端结构域（氨基酸182-206）。AA 182 -206与至少两种常见的人类组织相容性白细胞抗原（HLA）分子（HLA-A1和B8）相关，克隆频率为每10（-5）至10（-6）个脾淋巴细胞中有1个CTL。我们的数据表明，淋巴器官可能是体内激活的HIV特异性CTL的主要储库。此外，发现NEF的羧基末端结构域在几种HIV毒株中是保守的。因此，我们的发现对于进一步开发HIV疫苗具有重要意义。
Cytotoxic T lymphocytes (CTL) specific for human immunodeficiency virus (HIV) proteins have been analyzed in lymphoid organs from seropositive patients. Indeed, an active HIV replication coexists with a major CD8+ lymphocytic infiltration in these organs. We have shown in a previous report that HIV-seropositive patients lungs were infiltrated by HIV specific CD8+ lymphocytes. In the present report, we show that HIV-specific CTL responses can also be detected in lymph nodes and spleens, and were mainly directed against the ENV, GAG, and NEF HIV-1 proteins. The primary NEF-specific CTL responses were further characterized by epitope mapping. Determination of epitope-specific CTL frequencies were performed by limiting dilution analysis. Our results indicated that, in addition to the central region of NEF (AA66-148), a new immunodominant region is recognized by CTL. This region corresponds to the carboxyl-terminal domain of NEF (amino acids 182-206). AA182-206 is recognized in association with at least two common human histocompatibility leukocyte antigen (HLA) molecules (HLA-A1 and B8), with clonal frequencies of one CTL per 10(-5) to 10(-6) splenic lymphocytes. Our data indicate that lymphoid organs may represent a major reservoir for in vivo activated HIV-specific CTL. Furthermore, the carboxyl-terminal domain of NEF was found to be conserved among several HIV strains. Therefore, our finding is of interest for further HIV vaccines development.
Morikawa,H;K.Sugino;Y.Hayashi;J.Takeda;M.Senda;A.Hirai;Y.Yamada：生物/技术。
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