Downmodulation of antigen presentation by H2-O in B cell lines and primary B lymphocytes
Downmodulation of antigen presentation by H2-O in B cell lines and primary B lymphocytes
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DOI：
10.1002/immu.200310015
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发表时间：
2003-02-01
影响因子：
5.4
通讯作者：
Hämmerling, GJ
中科院分区：
文献类型：
--
作者：
Brocke, P;Armandola, E;Hämmerling, GJ
肽装载到 MHC II 类分子上发生在沿着内吞途径的内体区室中。在那里，辅助分子 H2-M 的催化功能促进了装载，这有助于将 II 类分子凹槽中的恒定链衍生的 CLIP 肽交换为抗原肽。 H2-O 是 II 类途径特有的另一种辅助分子，被发现与 H2-M 紧密相关并在 B 细胞中选择性表达。使用稳定的 H2-O 核酶反义转染子、H2-O 过表达鼠 B 细胞系和 H2-O 转基因小鼠，我们研究了 H2-O 对抗原呈递的影响。结果表明，向一组 T 细胞杂交瘤呈递多种外源蛋白抗原取决于呈递抗原的 B 细胞中的 H2-O 水平。因此，增加的 H2-O 表达下调，而降低的 H2-O 水平则增强表达。 H2-O 也减少了内源抗原的呈递。尽管对抗原呈递有显着影响，但从 A(b) 分子洗脱的肽的质谱图谱在表达不同 H2-O 水平的细胞中非常相似。使用药物氯喹研究了 H2-O 抑制活性的细胞内位置，该药物可防止内吞途径酸化。观察结果表明，H2-O 主要抑制早期内体区室中的抗原呈递。因此，H2-O 似乎使肽负载偏向晚期内体/溶酶体区室。这可能有利于 B 细胞受体摄取抗原的呈递。
Peptide loading onto MHC class II molecules takes place in endosomal compartments along the endocytic pathway. There, loading is facilitated by the catalytic function of the accessory molecule H2-M, which helps to exchange the invariant chain-derived CLIP peptide in the groove of class II molecules for antigenic peptide. H2-O is another accessory molecule specific to the class II pathway, which is found tightly associated with H2-M and selectively expressed in B cells. Using stable H2-O ribozyme-antisense transfectants, H2-O overexpressing murine B cell lines, and H2-O-transgenic mice, we investigated the effects of H2-O on antigen presentation. The results show that presentation of a variety of exogenous protein antigens to a panel of T cell hybridomas depended on the levels of H2-O in the antigenpresenting B cells. Thus, increased H2-O expression downmodulated, whereas reduced H2-O levels, enhanced presentation. Presentation of endogenous antigen was also diminished by H2-O. Despite the pronounced effects on antigen presentation, the mass spectrometric profiles of peptides eluted from A(b) molecules were very similar in cells expressing different H2-O levels. The intracellular location of H2-O inhibitory activity was investigated with the drug chloroquine, which prevents acidification of the endocytic pathway. The observations indicate that H2-O predominantly inhibits antigen presentation in early endosomal compartments. Thus, H2-O appears to skew peptide loading to late endosomal/lysosomal compartments. This may favor presentation of antigens taken up by the B cell receptor.