Isaguliants M G, Gudima S O, Ivanova O V, Levi M, Hinkula J, Garaev M M, Kochetkov S N, Wahren B
D. I. Ivanovsky Institute of Virology, Moscow, Russia.
AIDS Res Hum Retroviruses. 2000 Sep 1;16(13):1269-80. doi: 10.1089/08892220050117032.
Genetic immunization may be one way to prime individuals for a subsequent broad anti-HIV-1 immune response. Reverse transcriptase of HIV-1 (RT) presents a selective target for attempts to arrest replication of HIV-1. Rabbits immunized with a plasmid carrying the gene for reverse transcriptase HIV-1 (RT DNA) developed potent antibody and cellular responses to the gene product. The immunogenic properties of RT DNA and recombinant reverse transcriptase were compared in rabbits. The specific immune responses were similar to those reported previously for HIV-1 infected humans. The array of B and T cell epitopes recognized in RT DNA-immunized rabbits was broader than in rabbits immunized with the recombinant RT. We localized seven novel B and T cell epitopes and concordance between B cell and helper T cell epitopes was observed. B cell epitopes of RT induced proliferation of peripheral blood mononuclear cells and were active as helper T cell epitopes. T cell-proliferative responses to the epitopes of RT preceded or paralleled the production of antibodies of the same specificity. Subdomains of reverse transcriptase involved in the enzymatic activity of RT were highly immunogenic. Anti-RT IgG partially inhibited reverse transcription in vitro.
基因免疫可能是使个体引发后续广泛抗HIV-1免疫反应的一种方法。HIV-1的逆转录酶（RT）是试图阻止HIV-1复制的一个选择性靶点。用携带HIV-1逆转录酶基因的质粒（RT DNA）免疫的兔子对该基因产物产生了强烈的抗体和细胞反应。在兔子中比较了RT DNA和重组逆转录酶的免疫原性。特异性免疫反应与先前报道的HIV-1感染人类的反应相似。在RT DNA免疫的兔子中识别出的B和T细胞表位阵列比用重组RT免疫的兔子更广泛。我们定位了七个新的B和T细胞表位，并观察到B细胞和辅助性T细胞表位之间的一致性。RT的B细胞表位诱导外周血单核细胞增殖，并作为辅助性T细胞表位具有活性。对RT表位的T细胞增殖反应先于或与相同特异性抗体的产生平行。参与RT酶活性的逆转录酶亚结构域具有高度免疫原性。抗RT IgG在体外部分抑制逆转录。
