Macagno A, Gilliet M, Sallusto F, Lanzavecchia A, Nestle F O, Groettrup M
Research Department Cantonal Hospital St. Gall, St. Gallen, Switzerland.
Eur J Immunol. 1999 Dec;29(12):4037-42. doi: 10.1002/(SICI)1521-4141(199912)29:12<4037::AID-IMMU4037>3.0.CO;2-T.
Dendritic cells (DC) are highly specialized professional antigen presenting cells which are pivotal for the initiation and control of the cytotoxic T cell response. Upon stimulation by cytokines, bacteria, or CD40L DC undergo a maturation process from an antigen-receptive state to a state of optimal stimulation of T cells. We investigated the composition of proteasomes of DC derived from human peripheral blood monocytes before and after stimulation by CD40L, LPS, or proinflammatory cytokines (TNF-alpha + IL-6 + IL-1beta). Immunoprecipitation of proteasomes and analysis on two-dimensional gels revealed that during maturation the inducible proteasome subunits LMP2, LMP7, and MECL-1 are up-regulated and that the neosynthesis of proteasomes is switched exclusively to the production of immunoproteasomes containing these subunits. The proteasome regulator PA28 is markedly up-regulated in mature DC and in addition a so - far unidentified 21-kDa protein co-precipitates with the proteasome in LPS - stimulated DC. These changes in proteasome composition may be functionally linked to special properties of DC like MHC class I up-regulation or cross-priming. Our findings imply that the spectrum of class I-bound peptides may change after DC maturation which could be relevant for the design of DC - based vaccines.
树突状细胞（DC）是高度专业化的专职抗原呈递细胞，在细胞毒性T细胞反应的启动和控制中起关键作用。在细胞因子、细菌或CD40L的刺激下，DC经历从抗原接受状态到T细胞最佳刺激状态的成熟过程。我们研究了来自人外周血单核细胞的DC在受到CD40L、LPS或促炎细胞因子（TNF-α + IL-6 + IL-1β）刺激前后蛋白酶体的组成。蛋白酶体的免疫沉淀和二维凝胶分析显示，在成熟过程中，可诱导的蛋白酶体亚基LMP2、LMP7和MECL-1上调，并且蛋白酶体的新合成完全转向含有这些亚基的免疫蛋白酶体的产生。蛋白酶体调节剂PA28在成熟DC中明显上调，此外，在LPS刺激的DC中，一种迄今未鉴定的21 kDa蛋白与蛋白酶体共沉淀。蛋白酶体组成的这些变化可能在功能上与DC的特殊特性如MHC I类上调或交叉呈递相关。我们的研究结果表明，DC成熟后I类结合肽的谱可能会发生变化，这可能与基于DC的疫苗设计有关。
