Selective modulation of the major histocompatibility complex class II antigen presentation pathway following B cell receptor ligation and protein kinase C activation

Selective modulation of the major histocompatibility complex class II antigen presentation pathway following B cell receptor ligation and protein kinase C activation
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DOI:
10.1074/jbc.272.6.3641
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发表时间:
1997-02-07
影响因子:
4.8
通讯作者:
Davoust, J
Davoust, J
中科院分区:
生物学2区
文献类型:
--
作者:
Barois, N;Forquet, F;Davoust, J

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我们注意到,B细胞受体连接或佛波醇12-肉豆蔻酸酯13-乙酸酯处理诱导含有主要组织相容性复合物(MHC)II类和不变链(Ii)的胞内囊泡,并增加与II类分子共免疫沉淀的跨膜p12 Ii片段的量。为了确定蛋白激酶C激活对MHC II类呈递途径的影响,我们分析了Ii的亚细胞分布,SDS稳定形式的II类分子的诱导,以及它们呈递不同抗原的能力。Ii链可视化与管腔和细胞质定向抗体出现在早期的内体隔室转铁蛋白在佛波醇12-肉豆蔻酸酯13-乙酸酯治疗,而跨膜Ii降解产物相当于p12 Ii片段共定位与B细胞受体内化后交联。蛋白激酶C激活延迟了SDS稳定形式的II类分子的形成,并减少了需要新合成的II类α β-Ii复合物的抗原决定簇的呈递。这些数据表明,B细胞活化影响与生物合成途径交叉的内体区室中的Ii加工和MHC II类肽加载。
We noticed that B cell receptor ligation or phorbol 12-myristate 13-acetate treatment induced intracellular vesicles containing major histocompatibility complex (MHC) class II and invariant chain (Ii), and increased the amount of transmembrane p12 Ii fragments coimmunoprecipitated with class II molecules. To determine the influence of protein kinase C activation on the MHC class II presentation pathway, we analyzed the subcellular distribution of Ii, the induction of SDS-stable forms of class II molecules, and their ability to present different antigens. Ii chains visualized with luminal and cytoplasmic directed antibodies appeared in early endosomal compartments accessible to transferrin in response to phorbol 12-myristate 13-acetate treatment, whereas transmembrane Ii degradation products equivalent to the p12 Ii fragments were colocalized with the B cell receptors internalized after cross-linking. Protein kinase C activation delayed in parallel the formation of SDS-stable forms of class II molecules and reduced the presentation of antigenic determinants requiring newly synthesized class II alpha beta-Ii complexes. These data indicate that B cell activation affects Ii processing and MHC class II peptide loading in endosomal compartments intersecting the biosynthetic pathway.