The nonclassical immune surveillance for ERAAP function.

The nonclassical immune surveillance for ERAAP function.
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ERAAP功能的非经典免疫监视。

DOI:
10.1016/j.coi.2021.05.008
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发表时间:
2021-06
影响因子:
7
通讯作者:
Shastri N
Shastri N
中科院分区:
医学2区
文献类型:
--
作者:
Guan J;Peske JD;Taylor JA;Shastri N

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MHC-I类分子在细胞表面呈递的多肽库对于细胞内病原体和转化细胞的免疫监测是必不可少的。这一肽库的产生严重依赖于与抗原处理相关的内质网氨基肽酶(ERAAP)。ERAAP功能的丧失会导致产生一个被严重破坏的多肽库,包括许多新的和免疫原性多肽。值得注意的是,ERAAP-KO细胞上的这些新肽中的很大一部分是由非经典的MHC Ib分子Qa-1b提出的。一种免疫优势的Qa-1b限制性新肽被独特的CD8+T细胞群识别,显示出常规细胞毒性T细胞和非传统先天T细胞的特征。虽然仍有许多未被发现的地方,但我们在这里总结了我们实验室在非经典MHC Ib分子及其不寻常的同源T细胞介导的ERAAP功能的重要免疫监视方面的最新发现。
The peptide repertoire presented by MHC class I molecules on the cell surface is essential for the immune surveillance of intracellular pathogens and transformed cells. The generation of this peptide repertoire is critically dependent on the endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP). Loss of ERAAP function leads to the generation of a profoundly disrupted peptide repertoire including many novel and immunogenic peptides. Strikingly, a large fraction of these novel peptides on ERAAP-KO cells are presented by the nonclassical MHC Ib molecule, Qa-1b. One immunodominant Qa-1b-restricted novel peptide is recognized by a unique CD8+ T cell population showing features of both conventional cytotoxic T cells and unconventional innate-like T cells. While much remains to be uncovered, here we summarize the latest discoveries of our lab on the important immune surveillance of ERAAP function mediated by nonclassical MHC Ib molecules and their unusual cognate T cells.
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