PROTECTIVE IMMUNOGENICITY AND LYMPHOCYTE-T SPECIFICITY OF A TRIVALENT HYBRID PEPTIDE CONTAINING NH2-TERMINAL SEQUENCES OF TYPE-5, TYPE-6, AND TYPE-24 M-PROTEINS SYNTHESIZED IN TANDEM
PROTECTIVE IMMUNOGENICITY AND LYMPHOCYTE-T SPECIFICITY OF A TRIVALENT HYBRID PEPTIDE CONTAINING NH2-TERMINAL SEQUENCES OF TYPE-5, TYPE-6, AND TYPE-24 M-PROTEINS SYNTHESIZED IN TANDEM
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DOI：
10.1084/jem.166.3.647
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发表时间：
1987-09-01
影响因子：
15.3
通讯作者：
DALE, JB
中科院分区：
文献类型：
--
作者：
BEACHEY, EH;SEYER, JM;DALE, JB
研究了含有串联拷贝的5、6和24型M蛋白表位的杂合肽的保护性免疫原性。化学合成24型M蛋白的NH 2-末端肽，然后延伸至包括6型和5型M蛋白的NH 2-末端肽，产生在其COOH-末端含有半胱氨酸残基的34-残基杂合肽。当通过半胱氨酸残基结合到钥孔血蓝蛋白（KLH），在CFA中乳化，并注射到兔子，合成的混合物诱发调理素抗体对5型，6型和24型链球菌，而不刺激组织交叉反应性免疫。三价杂合物还能够在体内引发对M蛋白的每种天然血清型以及对体外合成杂合肽有应答的T淋巴细胞。引发的T细胞未能响应于杂合肽中所含的各个组分肽，这表明杂合肽赋予类似于M蛋白的相应血清型中的每个亚肽的呈现的构象。对串联杂交体中间所含的6型肽的活跃免疫应答表明，通过在脯氨酸残基之间的明智放置，潜在隐藏的肽容易被免疫系统接近。这些结果表明，合成的串联肽可以以一种方式进行定制，其中保护性表位的每个组分组可以被最佳地免疫可及和免疫原性。
The protective immunogenicity of a hybrid peptide containing tandem copies of types 5, 6, and 24 M protein epitopes was investigated. An NH2-terminal peptide of type 24 M protein was chemically synthesized and then extended to include NH2-terminal peptides of types 6 and 5 M proteins yielding a 34-residue hybrid peptide containing a cysteine residue at its COOH-terminus. When conjugated via the cysteine residue to keyhole limpet hemocyanin (KLH), emulsified in CFA, and injected into rabbits, the synthetic hybrid evoked opsonic antibodies against types 5, 6, and 24 streptococci without stimulating tissue crossreactive immunity. The trivalent hybrid also was capable of priming T lymphocytes in vivo that responded to each of the native serotypes of M protein as well as to the synthetic hybrid peptide in vitro. The primed T cells failed to respond to the individual component peptides contained in the hybrid peptide, suggesting that the hybrid peptide confers conformations resembling the presentations of each of the subpeptides in the respective serotypes of M protein. The brisk immune responses to the type 6 peptide contained in the middle of the tandem hybrid indicates that with judicious placement between proline residues, potentially hidden peptides are readily accessible to the immune system. These results suggest that synthetic tandem peptides can be tailored in a fashion in which each of the component sets of protective epitopes can be made optimally immunoaccessible and immunogenic.