The intracellular assembly of antigenic-peptide-class II complexes.

S K Pierce, J M Green, A E Faassen, X Xu, W Song, H Cho, P Schafer, T Psaradellis, N Wagle, J Kim
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Abstract

The immune system employs remarkable strategies to ensure that foreign antigens, from the most complex pathogens to the simplest proteins, are displayed on the surfaces of cells which are targets of T lymphocyte recognition. At the heart of these strategies is the molecular transformation of a soluble protein antigen to a complex of a small peptide containing the antigenic determinant bound to a cell surface Major Histocompatibility Complex class I or class II protein. This process is termed antigen presentation. Progress in a variety of laboratories over the last several years has yielded a wealth of information about the molecular mechanisms underlying antigen presentation, providing potential new approaches to vaccine design. Here we describe recent studies in our laboratory aimed at elucidating the intracellular site in B lymphocytes in which antigenic peptide-class II complexes are assembled for recognition by helper T cells and the regulation of this assembly process. Our results suggest that processed antigen-class II complexes are assembled in a unique compartment in the endocytic route which contains all the necessary cellular and molecular machinery for assembly and that B cells regulate the assembly process in response to external and internal signals.

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II类抗原肽复合物的细胞内组装。
免疫系统采用非凡的策略来确保外来抗原,从最复杂的病原体到最简单的蛋白质,显示在T淋巴细胞识别的目标细胞表面。这些策略的核心是可溶性蛋白抗原的分子转化为含有抗原决定因子的小肽复合物,该复合物与细胞表面主要组织相容性复合物I类或II类蛋白结合。这个过程称为抗原提呈。在过去几年中,各种实验室的进展已经产生了关于抗原呈递的分子机制的丰富信息,为疫苗设计提供了潜在的新方法。在这里,我们描述了我们实验室最近的研究,旨在阐明B淋巴细胞中抗原肽II类复合物组装以供辅助T细胞识别的细胞内位点以及该组装过程的调节。我们的研究结果表明,经过加工的II类抗原复合物在内吞途径中在一个独特的室中组装,该室包含组装所需的所有细胞和分子机制,B细胞根据外部和内部信号调节组装过程。
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