Trafficking of the Igα/Igβ heterodimer with membrane Ig and bound antigen to the major histocompatibility complex class II peptide-loading compartment

Trafficking of the Igα/Igβ heterodimer with membrane Ig and bound antigen to the major histocompatibility complex class II peptide-loading compartment
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DOI:
10.1074/jbc.274.16.11439
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发表时间:
1999-04-16
影响因子:
4.8
通讯作者:
Song, WX
Song, WX
中科院分区:
生物学2区
文献类型:
--
作者:
Brown, BK;Li, C;Song, WX

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抗原与B细胞抗原受体(BCR)的结合引发两个主要的细胞事件。首先,通过抗原交联后,BCR诱导信号转导级联,导致与B细胞活化相关的许多基因的转录。第二,BCR内化并将抗原递送至加工区室,其中加工的抗原肽被加载到主要组织相容性复合体(MHC)II类分子上以呈递给T辅助细胞。BCR由膜IG(mIG)和IG α/ IG β异源二聚体(IG α/IG β)组成。已表明BCR的信号转导组分IG α/IG β在抗原加工中发挥作用。为了了解IG α/IG β在抗原转运中的功能,我们研究了IG α/IG β的细胞内转运途径。我们表明,在抗原结合的情况下,IG α/IG β组成型交通与米格从质膜,通过早期内涵体,MHC II类肽装载室。交联BCR不会改变运输途径;然而,它加速了IG α/IG β向MHC II类肽装载区室的运输。这表明IG α/IG β异源二聚体通过整个抗原转运途径参与BCR介导的抗原转运。
The binding of antigen to the B cell antigen receptor (BCR) initiates two major cellular events. First, upon cross linking by antigen, the BCR induces signal transduction cascades leading to the transcription of a number of genes associated with B cell activation. Second, the BCR internalizes and delivers antigens to processing compartments, where processed antigenic peptides are loaded onto major histocompatibility complex (MHC) class II molecules for presentation to T helper cells. The BCR consists of membrane Ig (mIg) and Ig alpha/ Ig beta heterodimer (Ig alpha/Ig beta). The Ig alpha/Ig beta, the signal transducing component of the BCR, has been indicated to play a role in antigen processing. In order to understand the function of the Ig alpha/Ig beta in antigen transport, we studied the intracellular trafficking pathway of the Ig alpha/Ig beta. We show that in the absence of antigen binding, the Ig alpha/Ig beta constitutively traffics with mig from the plasma membrane, through the early endosomes, to the MHC class II peptide-loading compartment. Cross-linking the BCR does not alter the trafficking pathway; however, it accelerates the transport of the Ig alpha/Ig beta to the MHC class II peptide-loading compartment. This suggests that the Ig alpha/Ig beta heterodimer is involved in BCR-mediated antigen transport through the entire antigen transport pathway.