Polysaccharide processing and presentation by the MHCII pathway
Polysaccharide processing and presentation by the MHCII pathway
复制标题
DOI：
10.1016/j.cell.2004.05.001
复制
发表时间：
2004-05-28
期刊：
影响因子：
64.5
通讯作者：
Kasper, DL
中科院分区：
文献类型：
--
作者：
Cobb, BA;Wang, O;Kasper, DL
适应性免疫系统通过抗原呈递细胞（APCs）和T细胞的联合作用发挥功能。具体而言，I类主要组织相容性复合体向CD8(+) T细胞呈递抗原仅限于来自细胞内病原体的蛋白酶体产生的肽段，而II类（MHCII）内吞途径仅将来自细胞外病原体的蛋白水解肽段呈递给CD4(+) T细胞。人们一直认为碳水化合物可独立于T细胞刺激免疫反应；然而，一些细菌荚膜中的两性离子多糖（ZPSs）能够激活CD4(+) T细胞。在此我们表明，ZPSs通过一种一氧化氮介导的机制被加工为低分子量碳水化合物，并通过MHCII内吞途径呈递给T细胞。此外，这些碳水化合物在APCs内与MHCII结合以便呈递给T细胞。我们的观察结果开始阐明一些碳水化合物通过激活T细胞诱导重要免疫反应的机制，这表明MHCII呈递模式发生了根本性转变。
The adaptive immune system functions through the combined action of antigen-presenting cells (APCs) and T cells. Specifically, class I major histocompatibility complex antigen presentation to CD8(+) T cells is limited to proteosome-generated peptides from intracellular pathogens while the class II (MHCII) endocytic pathway presents only proteolytic peptides from extracellular pathogens to CD4(+) T cells. Carbohydrates have been thought to stimulate immune responses independently of T cells; however, zwitterionic polysaccharides (ZPSs) from the capsules of some bacteria can activate CD4(+) T cells. Here we show that ZPSs are processed to low molecular weight carbohydrates by a nitric oxide-mediated mechanism and presented to T cells through the MHCII endocytic pathway. Furthermore, these carbohydrates bind to MHCII inside APCs for presentation to T cells. Our observations begin to elucidate the mechanisms by which some carbohydrates induce important immunologic responses through T cell activation, suggesting a fundamental shift in the MHCII presentation paradigm.