Leclerc C, Sedlik C, Lo-Man R, Charlot B, Rojas M, Dériaud E
Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France.
Eur J Immunol. 1995 Sep;25(9):2533-8. doi: 10.1002/eji.1830250919.
The use of universally immunogenic T cell epitopes, such as those identified in tetanus toxin or malaria circumsporozoite protein, could represent a major improvement in the development of synthetic vaccines. However, one limitation of this approach is the lack of T cell cross-reactivity between the vaccine and the pathogen. To determine whether the memory B cell response elicited by immunization with a synthetic peptide containing a B cell epitope linked to a T cell epitope can be restimulated by the same B cell epitope linked to different T cell epitope(s), we used a synthetic peptide which contains non-overlapping B and T cell determinants from hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV). The results of this study clearly show that primed T cells can increase the antibody response against a B cell epitope linked to the priming T cell determinant. However, the antibody response obtained was weaker than that obtained after two injections of the peptide containing both B and T cell epitopes, showing the important role played by memory B cells in secondary antibody responses. Moreover, a strong antibody response against the B cell epitope was elicited by boosting mice with the B cell epitope linked to a heterologous carrier, thus demonstrating that a strong B cell memory response can be revealed in the absence of primed T cells. These results therefore provide new important information for the design of synthetic or recombinant vaccines.
使用普遍具有免疫原性的T细胞表位,例如在破伤风毒素或疟疾环子孢子蛋白中鉴定出的那些,可能代表合成疫苗开发中的一项重大进展。然而,这种方法的一个局限性是疫苗与病原体之间缺乏T细胞交叉反应性。为了确定用含有与T细胞表位相连的B细胞表位的合成肽免疫引发的记忆B细胞反应是否能被与不同T细胞表位相连的相同B细胞表位重新刺激,我们使用了一种合成肽,其包含来自乙型肝炎病毒(HBV)的乙型肝炎表面抗原(HBsAg)的非重叠B细胞和T细胞决定簇。这项研究的结果清楚地表明,致敏T细胞可以增强针对与致敏T细胞决定簇相连的B细胞表位的抗体反应。然而,获得的抗体反应比两次注射含有B细胞和T细胞表位的肽后获得的反应弱,这表明记忆B细胞在二次抗体反应中发挥的重要作用。此外,用与异源载体相连的B细胞表位对小鼠进行加强免疫可引发针对该B细胞表位的强烈抗体反应,从而证明在没有致敏T细胞的情况下也能揭示强烈的B细胞记忆反应。因此,这些结果为合成或重组疫苗的设计提供了新的重要信息。