Peptide transporter TAP mediates between competing antigen sources generating distinct surface MHC class I peptide repertoires
Peptide transporter TAP mediates between competing antigen sources generating distinct surface MHC class I peptide repertoires
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DOI：
10.1002/eji.201141836
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发表时间：
2011-11-01
影响因子：
5.4
通讯作者：
van Hall, Thorbald
中科院分区：
文献类型：
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作者：
Oliveira, Claudia C.;Querido, Bianca;van Hall, Thorbald
我们最近描述了一类与tap无关的肽表位，这些表位是由在经典MHC I类（MHC-I）途径中具有加工缺陷的细胞选择性呈现的。在这里，我们研究了内质网驻留神经酰胺合成酶Trh4作为这些新抗原的原型例子，发现适度抑制TAP允许Trh4肽在细胞表面呈现。WT细胞中缺乏这种肽与Trh4/D-b复合物的结合或稳定性无关，也与MHC-I重链的可用性无关，而是与抗原的有限表达有关。要在WT上达到与tap缺陷细胞相当的肽显示，需要高水平的抗原。我们的数据表明，在常规加工过程中，tap转运肽在内质网中的正常流入为来自其他加工途径的肽创造了一个有效的屏障。TAP功能的损伤通常在癌症和病毒感染细胞中发现，降低了这种耐药性，允许MHC-I呈现其他肽源。
We recently described a category of TAP-independent peptide-epitopes that are selectively presented by cells with processing defects in the classical MHC class I (MHC-I) pathway. Here, we studied the ER-resident ceramide synthase Trh4 as a prototypic example of these neo-antigens and found that moderate inhibition of TAP permits cell surface presentation of the Trh4 peptide. The absence of this peptide from WT cells was not related to the binding or stability of the Trh4/D-b complexes, or to the availability of MHC-I heavy chains, but rather to the limited expression of the antigen. Strongly elevated antigen levels were needed to reach comparable peptide display on WT as on TAP-deficient cells. Our data suggest that the normal influx of TAP-transported peptides in the ER during routine processing creates an efficient barrier for peptides from alternative processing routes. Impairment of TAP function, as commonly found in cancers and virus-infected cells, lowers this resistance allowing for MHC-I presentation of other peptide sources.