DEVELOPMENT OF HIGH POTENCY UNIVERSAL DR-RESTRICTED HELPER EPITOPES BY MODIFICATION OF HIGH-AFFINITY DR-BLOCKING PEPTIDES
DEVELOPMENT OF HIGH POTENCY UNIVERSAL DR-RESTRICTED HELPER EPITOPES BY MODIFICATION OF HIGH-AFFINITY DR-BLOCKING PEPTIDES
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DOI：
10.1016/s1074-7613(94)80017-0
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发表时间：
1994-12-01
期刊：
影响因子：
32.4
通讯作者：
GREY, HM
中科院分区：
文献类型：
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作者：
ALEXANDER, J;SIDNEY, J;GREY, HM
通过在聚丙氨酸骨架内引入不同DR基序的锚残基而工程化的泛DR结合肽结合10个测试的DR分子中的10个，在大多数情况下，亲和力在纳摩尔范围内。由于小的甲基暴露远T细胞识别，这些肽是不良的免疫原，但DR限制性抗原呈递的有效阻断剂。在可用于T细胞识别的位置处引入庞大且带电的残基产生了非常强大的泛DR表位肽（PADRE）。这些肽在体外从人外周血单核细胞（PBMC）引起强有力的应答。因为这些细胞也对某些小鼠II类等位基因交叉反应，我们也可以证明PADRE肽在体内是有活性的。在它们引发T辅助的能力的一个例子中，它们比天然T细胞表位强大约1000倍。我们建议PADRE肽可能是有用的亚单位疫苗的发展。
Pan DR-binding peptides engineered by introducing anchor residues for different DR motifs within a polyalanine backbone bound 10 of 10 DR molecules tested, with affinities, in most cases, in the nanomolar range. Because of the small methyl group exposed far T cell recognition, these peptides were poor immunogens but effective blockers of DR-restricted antigen presentation. Introduction of bulky and charged residues at positions accessible for T cell recognition yielded extremely powerful Pan DR epitope peptides (PADRE). These peptides elicited powerful responses in vitro from human peripheral blood mononuclear cells (PBMC). Because these cells also cross-react on certain mouse class II alleles, we could also demonstrate that PADRE peptides are active in vivo. In one example of their capacity to elicit T help, they were approximately 1000 times more powerful than natural T cell epitopes. We propose that PADRE peptides may be useful in the development of subunit vaccines.