Immunogenicity of recombinant chaperone-complexed antigens

重组伴侣复合抗原的免疫原性

• 批准号: 5154218
• 负责人: Professor Dr. Reinhold Schirmbeck
• 金额: --
• 依托单位: Klinik für Innere Medizin I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 1998
• 资助国家: 德国
• 起止时间: 1997-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5154218?language=en
• 关键词: Immunogenicity; recombinant; chaperone; complexed; antigens

We will study the immunogenicity of antigen/hsp complexes that are either expressed (as endogenous complexes) by antigen-presenting cells (APC), or taken up by APC as exogenous complexes, processed and presented to lymphocytes. Methods for the production, purification and characterization of recombinant hsp73- fusion antigen complexes will be refined. The cell biology of processing exogenous or endogenous hsp/antigen complexes for MHC class I-restricted epitope presentation to cytotoxic T lymphocytes (CTL) will be studied. The main focus will be on the intracellular traffic of exogenous or endogenous hsp/antigen complexes, the subcellular site at which processing takes place, the site and kinetic of the generation of presentation-competent MHC class I molecules, and the proteolytic system(s) involved. Attempts will be made to facilitate proteolytic processing of hsp-bound recombinant fusion antigen by flanking the relevant epitopes with cathepsin-sensitive cleavage sites. These in vitro studies will be complemented by in vivo studies that will elucidate priming of humoral and cellular immune responses in vivo by DNA- or protein-based vaccines containing hsp/antigen complexes. The project makes an effort to integrate the in vitro study of the cell biology of processing and presentation with the in vivo study of the immunogenicity of hsp/antigen complexes that are a fascinating, novel approach of T cell-stimulating vaccines based on a natural adjuvant.

我们将研究抗原/热休克蛋白复合物的免疫原性，这些复合物要么由抗原呈递细胞（APC）表达（作为内源性复合物），要么由APC作为外源性复合物吸收，加工并呈递给淋巴细胞。重组热休克蛋白73融合抗原复合物的生产，纯化和表征方法将得到改进。本论文将研究加工外源性或内源性hsp/抗原复合物以将MHC I类限制性表位呈递给细胞毒性T淋巴细胞（CTL）的细胞生物学。主要的焦点将是外源性或内源性热休克蛋白/抗原复合物的细胞内交通，加工发生的亚细胞位点，呈递能力的MHC I类分子的产生的位点和动力学，以及所涉及的蛋白水解系统。将尝试通过用组织蛋白酶敏感的切割位点侧接相关表位来促进hsp结合的重组融合抗原的蛋白水解加工。这些体外研究将通过体内研究来补充，体内研究将阐明含有HSP/抗原复合物的DNA或蛋白质疫苗在体内引发的体液和细胞免疫应答。该项目致力于将加工和呈递的细胞生物学的体外研究与热休克蛋白/抗原复合物的免疫原性的体内研究相结合，热休克蛋白/抗原复合物是基于天然佐剂的T细胞刺激疫苗的一种迷人的新方法。