Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules
Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules
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DOI：
10.1074/jbc.m011547200
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发表时间：
2001-05-18
影响因子：
4.8
通讯作者：
Srivastava, PK
中科院分区：
文献类型：
--
作者：
Binder, RJ;Blachere, NE;Srivastava, PK
这里报道的研究承担在细胞质中的事件，导致在抗原加工和主要组织相容性复合体（MHC）I分子的呈递过程中肽的运输。我们已经将游离的抗原肽或与血清白蛋白或与细胞质热休克蛋白hsp90（及其内质网同源物gp96）或hsp70结合的抗原肽引入活细胞的细胞质中，并通过适当的MHC I分子监测肽的呈递。实验表明，（i）引入胞质溶胶中的游离肽或血清白蛋白结合肽以远低于由任何测试的热休克蛋白陪伴的肽的效率成为MHC I分子的配体，和（ii）用脱氧精胍菌素（deoxyspergualin）（一种以表观特异性结合hsp70和hsp90的药物）处理细胞，消除细胞通过MHC I分子呈递抗原肽的能力，并且将额外的HSP 70引入胞质溶胶克服了这种消除。这些结果首次提示了胞质分子伴侣在抗原加工中的功能作用。
The studies reported here bear on the events in the cytosol that lead to trafficking of peptides during antigen processing and presentation by major histocompatibility complex (MHC) I molecules. We have introduced free antigenic peptides or antigenic peptides bound to serum albumin or to cytosolic heat shock proteins hsp90 (and its endoplasmic reticular homologue gp96) or hsp70 into the cytosol of living cells and have monitored the presentation of the peptides by appropriate MHC I molecules. The experiments show that (i) free peptides or serum albumin-bound peptides, introduced into the cytosol, become ligands of MHC I molecules at a far lower efficiency than peptides chaperoned by any of the heat shock proteins tested and (ii) treatment of cells with deoxyspergualin, a drug that binds hsp70 and hsp90 with apparent specificity, abrogates the ability of cells to present antigenic peptides through MHC I molecules, and introduction of additional hsp70 into the cytosol overcomes this abrogation. These results suggest for the first time a functional role font cytosolic chaperones in antigen processing.