Intracellular trafficking of HLA-E and its regulation.
Intracellular trafficking of HLA-E and its regulation.
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DOI：
10.1084/jem.20221941
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发表时间：
2023-08-07
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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了解人类白细胞抗原-E的免疫功能的独特特征以指导未来的临床开发需要对人类白细胞抗原-E转运的详细知识。他等人。描述细胞内人类白细胞抗原E的基本贩运模式，以及这种贩运是如何受到管制的。在疫苗模型中，MHC-E限制性CD8+T细胞反应在控制猴免疫缺陷病毒(SIV)感染方面的有效性的发现引起了人们的兴趣。利用人类MHC-E(HLAE)限制性CD8+T细胞反应开发疫苗和免疫疗法需要了解HLAE转运和抗原提呈的途径(S)，这是以前没有明确定义的。我们在这里表明，与经典的HLAI类不同，HLAI类在合成后迅速退出内质网(ER)，由于高亲和力多肽的供应有限，HLA-E在很大程度上被保留下来，并通过其细胞质尾巴进行进一步的微调。一旦到达细胞表面，人类白细胞抗原-E就不稳定，并被迅速内化。胞质尾部在促进人类白细胞抗原-E内化过程中起着至关重要的作用，从而导致其在晚期和再循环内小体中的富集性。我们的数据揭示了人类白细胞抗原-E独特的转运模式和微妙的调节机制，这有助于解释其异常的免疫学功能。
Understanding the unique features of immune functions of HLA-E to inform future clinical exploitation requires detailed knowledge of HLA-E transport. He et al. characterize the basic trafficking patterns of HLA-E within cells and how this trafficking is regulated. Interest in MHC-E–restricted CD8+ T cell responses has been aroused by the discovery of their efficacy in controlling simian immunodeficiency virus (SIV) infection in a vaccine model. The development of vaccines and immunotherapies utilizing human MHC-E (HLA-E)–restricted CD8+ T cell response requires an understanding of the pathway(s) of HLA-E transport and antigen presentation, which have not been clearly defined previously. We show here that, unlike classical HLA class I, which rapidly exits the endoplasmic reticulum (ER) after synthesis, HLA-E is largely retained because of a limited supply of high-affinity peptides, with further fine-tuning by its cytoplasmic tail. Once at the cell surface, HLA-E is unstable and is rapidly internalized. The cytoplasmic tail plays a crucial role in facilitating HLA-E internalization, which results in its enrichment in late and recycling endosomes. Our data reveal distinctive transport patterns and delicate regulatory mechanisms of HLA-E, which help to explain its unusual immunological functions.
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MTB衍生的抗原对人CD8+ T细胞的HLA-E依赖性表现。
影响因子：
15.3
作者：
Heinzel, Amy S;Grotzke, Jeff E;Lines, Rebecca A;Lewinsohn, Deborah A;McNabb, Andria L;Streblow, Daniel N;Braud, Veronique M;Grieser, Heather J;Belisle, John T;Lewinsohn, David M
通讯作者：
Lewinsohn, David M
DOI：
10.1126/science.aac9475
发表时间：
2016-02-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hansen SG;Wu HL;Burwitz BJ;Hughes CM;Hammond KB;Ventura AB;Reed JS;Gilbride RM;Ainslie E;Morrow DW;Ford JC;Selseth AN;Pathak R;Malouli D;Legasse AW;Axthelm MK;Nelson JA;Gillespie GM;Walters LC;Brackenridge S;Sharpe HR;López CA;Früh K;Korber BT;McMichael AJ;Gnanakaran S;Sacha JB;Picker LJ
通讯作者：
Picker LJ
影响因子：
30.5
作者：
Basha G;Omilusik K;Chavez-Steenbock A;Reinicke AT;Lack N;Choi KB;Jefferies WA
通讯作者：
Jefferies WA
DOI：
10.1084/jem.187.5.813
发表时间：
1998-03-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Borrego F;Ulbrecht M;Weiss EH;Coligan JE;Brooks AG
通讯作者：
Brooks AG
影响因子：
9.2
作者：
Braud, VM;Allan, DSJ;McMichael, AJ
通讯作者：
McMichael, AJ