Wagner Hermann, Heit Antje, Schmitz Frank, Bauer Stefan
Institute of Medical Microbiology, Immunology and Hygiene, Trogerstrasse. 9, 81675 Munich, Germany.
Curr Opin Biotechnol. 2004 Dec;15(6):538-42. doi: 10.1016/j.copbio.2004.09.006.
Compared to 'live' vaccines, the immunogenicity of 'split' vaccines based on recombinant antigen (Ag) is poor, presumably because exogeneous recombinant Ag fails to efficiently access the major histocompatibility complex (MHC) class I processing pathway needed for 'cross-presentation'. Here we discuss recent evidence that targeting ligands of the Toll-like receptor 9 together with proteinaceous Ag to the endosome of dendritic cells conveys immunogenicity to Ag similar in magnitude to 'live' vaccines that produce Ag. Enforced endocytosis of Ag together with the adjuvant effect of Toll-like receptor 9 ligands might be key for the efficient cross-presentation of exogeneous Ag as well as for effective cross-priming of MHC class I restricted CD8 T effector cells.
与“活”疫苗相比,基于重组抗原(Ag)的“裂解”疫苗的免疫原性较差,推测是因为外源性重组抗原无法有效进入“交叉呈递”所需的主要组织相容性复合体(MHC)I类加工途径。在此,我们讨论最近的证据,即靶向Toll样受体9的配体与蛋白质抗原一起递送至树突状细胞的内体,可赋予抗原与产生抗原的“活”疫苗相似程度的免疫原性。抗原的强制内吞作用以及Toll样受体9配体的佐剂效应可能是外源性抗原有效交叉呈递以及MHC I类限制性CD8 T效应细胞有效交叉启动的关键。