Partidos C D, Stanley C M, Steward M W
Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, U.K.
J Gen Virol. 1991 Jun;72 ( Pt 6):1293-9. doi: 10.1099/0022-1317-72-6-1293.
The immunogenicity of chimeric peptides produced by collinear synthesis to contain both T and B cell epitopes from the fusion protein and the haemagglutinin of measles virus was studied in mice. The T cell epitope used was from the fusion protein (residues 288 to 302), which has been shown to be promiscuous in its binding to mouse major histocompatibility complex molecules. This epitope was coupled by (i) a glycine-glycine spacer to a B cell epitope from the fusion protein (residues 404 to 414) and (ii) either its amino or carboxy terminus to a neutralizing antibody epitope from the haemagglutinin (residues 188 to 199). The results obtained show that such chimeric peptides can indeed function as complete immunogens in a range of mouse strains of different H-2 haplotype, and can induce the production of antibodies which bind to the fusion protein and to measles virus. Furthermore, it was shown that the orientation of the T cell epitope with respect to the B cell epitope had a significant effect upon the immunogenicity and antigenic specificity of the chimera. This work gives further support to the concept of rationally designed synthetic peptide vaccines.
研究了通过共线合成产生的嵌合肽的免疫原性,这些嵌合肽包含来自麻疹病毒融合蛋白和血凝素的T细胞和B细胞表位。所使用的T细胞表位来自融合蛋白(第288至302位氨基酸残基),该表位已被证明在与小鼠主要组织相容性复合体分子结合方面具有多态性。这个表位通过(i)一个甘氨酸-甘氨酸间隔区与来自融合蛋白的B细胞表位(第404至414位氨基酸残基)相连,以及(ii)其氨基或羧基末端与来自血凝素的中和抗体表位(第188至199位氨基酸残基)相连。所得结果表明,此类嵌合肽在一系列不同H-2单倍型的小鼠品系中确实可作为完全免疫原发挥作用,并可诱导产生与融合蛋白和麻疹病毒结合的抗体。此外,还表明T细胞表位相对于B细胞表位的方向对嵌合体的免疫原性和抗原特异性有显著影响。这项工作进一步支持了合理设计合成肽疫苗的概念。