The HSC73 molecular chaperone: involvement in MHC class II antigen presentation.

The HSC73 molecular chaperone: involvement in MHC class II antigen presentation.
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HSC73 分子伴侣:参与 MHC II 类抗原呈递。

DOI:
--
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发表时间:
1999
影响因子:
4.4
通讯作者:
B. Stockinger
B. Stockinger
中科院分区:
医学2区
文献类型:
--
作者:
Naveed N. Panjwani;O. Akbari;S. Garcia;Melanie I. Brazil;B. Stockinger

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热休克蛋白(HSP)是一种保守的蛋白质,其中许多蛋白质都具有不加选择性的肽结合和ATP酶偶联肽释放的能力。在本文中,我们表明,热休克同源蛋白(HSC)73,热休克蛋白70家族的组成型表达的成员,可能是一个候选人的分子伴侣活性内的MHC II类呈递途径。HSC 73在巨噬细胞中的表达被证明与MHC II类的表达重叠; HSC 73在巨噬细胞系的稳定转染子中的过表达显著增强了它们对外源性Ag的呈递,而不影响对加工独立肽的呈递。来自外源性来源的Ag被证明与巨噬细胞中的HSC 73相关联,并且这种关联对ATP处理敏感,并且被脱氧精胍菌素(deoxyspergualin)抑制,脱氧精胍菌素是一种免疫抑制剂,先前已被证明特异性结合HSC 73。此外,deoxyspergualin减少Ag呈递巨噬细胞在这些细胞中表达的HSC 73的量。这些数据与HSC 73在结合和保护肽免于广泛降解和/或促进肽转移至MHC II类分子的动力学中的潜在作用一致。
Heat shock proteins (HSP) are conserved proteins, many of which share the ability for indiscriminate peptide binding and ATPase-coupled peptide release. In this paper, we show that heat shock cognate protein (HSC)73, a constitutively expressed member of the HSP70 family, could be a candidate for chaperone activity within the MHC class II presentation pathway. HSC73 expression in macrophages was shown to overlap with expression of MHC class II; overexpression of HSC73 in stable transfectants of a macrophage line markedly enhanced their presentation of exogenous Ag without affecting presentation of processing independent peptide. Ag from an exogenous source was demonstrated to associate with HSC73 in macrophages, and this association was sensitive to ATP treatment and inhibited by deoxyspergualin, an immunosuppressive agent that has previously been shown to bind specifically to HSC73. Furthermore, deoxyspergualin reduced Ag presentation by macrophages in relation to the amount of HSC73 expressed in these cells. The data are consistent with a potential role for HSC73 in binding and protecting peptides from extensive degradation and/or facilitating the kinetics of peptide transfer to MHC class II molecules.
DOI: 10.1126/science.2756425
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期刊: SCIENCE
影响因子: 56.9
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DOI: --
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DOI: --
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