A strategy for making synthetic peptide vaccines.
A strategy for making synthetic peptide vaccines.
复制标题
制造合成肽疫苗的策略。
DOI：
10.1073/pnas.89.19.8995
复制
发表时间：
1992
影响因子：
11.1
通讯作者：
Onoé,K
中科院分区：
文献类型：
--
作者：
Ogasawara,K;Naruse,H;Itoh,Y;Gotohda,T;Arikawa,J;Kida,H;Good,RA;Onoé,K
我们已经确定了由鸽子细胞色素 c (p43-58) 残基 43-58 组成的合成肽的 Agretope（肽抗原与主要组织相容性复合物之间的接触位点）的 H-2 II 类等位基因特异性氨基酸基序。残基46和54充当抗原位，残基50和52充当表位（肽抗原与T细胞抗原受体之间接触的位点）。一般来说，聚集位和表位独立发挥作用。因此，表位中氨基酸的取代不会显着影响肽抗原与II类分子的结合。基于这些发现，通过将流感病毒血凝素的7个残基引入到p43-58类似物的框架成分残基43-46和54-58（包括先前在p43-58片段上确定的Ak或Ab的Aggretopes）中，制备了针对爱知流感（H3N2）病毒的合成肽疫苗。这些肽疫苗诱导辅助 T 细胞反应并产生对流感爱知血凝素具有特异性的抗体，但对携带 Ak 或 Ab 的小鼠中的主要组织相容性复合物结合框架不具有特异性。产生的抗体在体外中和爱知流感的感染性。目前的研究结果应该为制备有效且不产生副作用的肽疫苗提供基础。
We have determined the H-2 class II allele-specific amino acid motif of the agretope (the site of contact between the peptide antigen and the major histocompatibility complex) for a synthetic peptide composed of residues 43-58 of pigeon cytochrome c (p43-58). Residues 46 and 54 functioned as the agretope, and residues 50 and 52 functioned as the epitope (the site for contact between the peptide antigen and the T-cell antigen receptor). In general, agretopes and epitopes function independently. Thus, substitution of amino acids in the epitope does not significantly affect binding of the peptide antigen to a class II molecule. On the basis of these findings, synthetic peptide vaccines against influenza Aichi (H3N2) virus were prepared by introducing seven residues of the influenza virus hemagglutinin into the frame component residues 43-46 and 54-58 of p43-58 analogues including the agretopes for Ak or Ab previously determined on the p43-58 segment. These peptide vaccines induced both helper T-cell responses and production of antibodies that were specific for influenza Aichi hemagglutinin but not for the major histocompatibility complex binding frame in mice bearing Ak or Ab. The antibodies produced neutralize the infectivity of influenza Aichi in vitro. The present findings should provide a basis for preparing potent peptide vaccines that function without producing side effects.