ERAP1 functions override the intrinsic selection of specific antigens as immunodominant peptides, thereby altering the potency of antigen-specific cytolytic and effector memory T-cell responses.
ERAP1 functions override the intrinsic selection of specific antigens as immunodominant peptides, thereby altering the potency of antigen-specific cytolytic and effector memory T-cell responses.
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ERAP1 的功能超越了作为免疫显性肽的特定抗原的内在选择，从而改变了抗原特异性溶细胞和效应记忆 T 细胞反应的效力。
DOI：
10.1093/intimm/dxu078
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发表时间：
2014
影响因子：
4.4
通讯作者：
Amalfitano,Andrea
中科院分区：
文献类型：
--
作者：
Rastall,DavidPW;Aldhamen,YasserA;Seregin,SergeyS;Godbehere,Sarah;Amalfitano,Andrea
内质网氨肽酶1（ERAP 1）是适应性免疫系统的重要组成部分，其已被证明增加或减少MHC I类分子上的特异性肽的呈递。在这里，我们已经证明ERAP 1功能不仅在抗原衍生肽的呈递过程中很重要，而且这些功能还可以完全改变抗原衍生肽最终被选择为免疫显性T细胞表位。我们的研究结果表明，ERAP 1可能通过破坏表位来实现这一点，否则这些表位将在缺乏足够的ERAP 1功能的情况下成为免疫显性。我们进一步确定ERAP 1介导的对T细胞功能的影响是定性和定量的，通过证明ERAP 1功能的丧失将CTL杀伤重定向到不同的抗原衍生表位组，并增加抗原暴露引起的抗原特异性记忆T细胞的百分比。因此，我们的研究表明，正常的ERAP 1活性可以抑制对给定抗原应答的T效应记忆细胞的数量。这一独特的发现可能揭示了为什么某些ERAP 1单核苷酸多态性与几种自身免疫性疾病相关，例如，通过显着改变CD8+ T细胞对抗原衍生肽的记忆反应的稳健性和质量。
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a critical component of the adaptive immune system that has been shown to increase or decrease the presentation of specific peptides on MHC class I molecules. Here, we have demonstrated that ERAP1 functions are not only important during the presentation of antigen-derived peptides, but these functions can also completely change which antigen-derived peptides ultimately become selected as immunodominant T-cell epitopes. Our results suggest that ERAP1 may do this by destroying epitopes that would otherwise become immunodominant in the absence of adequate ERAP1 functionality. We further establish that ERAP1-mediated influences on T-cell functions are both qualitative and quantitative, by demonstrating that loss of ERAP1 function redirects CTL killing toward a different set of antigen-derived epitopes and increases the percent of antigen-specific memory T cells elicited by antigen exposure. As a result, our studies suggest that normal ERAP1 activity can act to suppress the numbers of T effector memory cells that respond to a given antigen. This unique finding may shed light on why certain ERAP1 single nucleotide polymorphisms are associated with several autoimmune diseases, for example, by significantly altering the robustness and quality of CD8+ T-cell memory responses to antigen-derived peptides.
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影响因子：
3.7
作者：
Tsai FJ;Lee YC;Chang JS;Huang LM;Huang FY;Chiu NC;Chen MR;Chi H;Lee YJ;Chang LC;Liu YM;Wang HH;Chen CH;Chen YT;Wu JY
通讯作者：
Wu JY
影响因子：
4.4
作者：
Aldhamen, Yasser Ali;Seregin, Sergey S.;Amalfitano, Andrea
通讯作者：
Amalfitano, Andrea
DOI：
10.1073/pnas.0609990104
发表时间：
2007-04-10
影响因子：
11.1
作者：
Belz, Gabrielle T.;Zhang, Lei;Davenport, Miles P.
通讯作者：
Davenport, Miles P.
影响因子：
9.1
作者：
Cho, Bon-A;Sim, Ji Hyun;Kim, Hang-Rae
通讯作者：
Kim, Hang-Rae
影响因子：
20.3
作者：
Helft, Julie;Jacquet, Alexandra;Lantz, Olivier
通讯作者：
Lantz, Olivier