Estaquier J, Gras-Masse H, Boutillon C, Ameisen J C, Capron A, Tartar A, Auriault C
Unité mixte INSERM U167-CNRS 624, Lille, France.
Eur J Immunol. 1994 Nov;24(11):2789-95. doi: 10.1002/eji.1830241132.
We report a new approach in peptide vaccine strategy based on combinatorial synthesis. A library of 7.5 x 10(5) related peptides, termed mixotope, was derived from the sequence of the third hypervariable domain (V3 loop) of the human immunodeficiency virus (HIV) envelope protein. This preparation induced a strong immune response in all syngeneic and outbred rodents tested. The response directed against the mixotope included antibodies, CD4+ T helper cells (TH1 and TH2) and CD8+ T cells. In rodents immunized with the mixotope, the T cell response directed against individual V3 peptide sequences (BRU, MN, RF, SF2, and ELI) as measured by T cell proliferation and interleukin (IL)-2 production, was found to be major histocompatibility complex haplotype-dependent. However, additional experiments performed in mice indicated that selectivity was less restrictive when using IL-3 secretion to explore T cell activation. This combinatorial antigen could be considered as a series of agretopic motifs framing a multiplicity of closely related epitopes for T cell recognition and able to elicit a T cell and B cell repertoire. This new construct may therefore provide a basis for the design of future vaccine strategies.
我们报告了一种基于组合合成的肽疫苗策略新方法。一个包含7.5×10⁵个相关肽的文库，称为混合表位，源自人类免疫缺陷病毒（HIV）包膜蛋白第三高变区（V3环）的序列。该制剂在所有测试的同基因和远交啮齿动物中均诱导出强烈的免疫反应。针对混合表位的反应包括抗体、CD4⁺辅助性T细胞（TH1和TH2）和CD8⁺T细胞。在用混合表位免疫的啮齿动物中，通过T细胞增殖和白细胞介素（IL）-2产生来测量的针对单个V3肽序列（BRU、MN, RF、SF2和ELI）的T细胞反应，发现是主要组织相容性复合体单倍型依赖性的。然而，在小鼠中进行的额外实验表明，当使用IL-3分泌来探索T细胞激活时，选择性限制较少。这种组合抗原可被视为一系列围绕多种密切相关表位的聚集基序，用于T细胞识别，并能够引发T细胞和B细胞库。因此，这种新构建体可能为未来疫苗策略的设计提供基础。
