Spotlight on TAP and its vital role in antigen presentation and cross-presentation.
Spotlight on TAP and its vital role in antigen presentation and cross-presentation.
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DOI：
10.1016/j.molimm.2021.12.013
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发表时间：
2022-03
影响因子：
3.6
通讯作者：
Blander, J. Magarian
中科院分区：
文献类型：
--
作者：
Mantel, Ian;Sadiq, Barzan A. A.;Blander, J. Magarian
关键词：
在 20 世纪 80 年代末和 90 年代初，对表面上负责肽穿过内质网 (ER) 膜易位的转运蛋白分子的寻找成功地发现了与抗原加工 (TAP) 蛋白相关的转运蛋白。 TAP 是由 TAP1 和 TAP2 组成的异二聚体复合物，它利用 ATP 将胞质肽跨膜转运到 ER 中。在 ER 中，它与其他成分一起形成肽装载复合物 (PLC)，该复合物指导将高亲和力肽装载到新生的主要组织相容性复合物 I 类 (MHC-I) 分子上，然后将其转运到细胞表面以呈递给 CD8+ T 细胞。在树突状细胞 (DC) 中交叉呈递过程中，TAP 在将肽转运至吞噬体和内体中也发挥着至关重要的作用。由于 TAP 在经典 MHC-I 呈递和交叉呈递中发挥着关键作用，其表达和功能常常受到多种类型的癌症和病毒的损害，以逃避细胞毒性 CD8 T 细胞的识别。在这里，我们回顾 TAP 的发现和功能，重点关注它在 DC 交叉表达中的作用。我们讨论了最近描述的非典型交叉呈递的紧急途径，该途径在 TAP 阻断后在 DC 中动员以恢复 CD8 T 细胞交叉引发。我们还讨论了癌细胞和病毒采用的各种策略来靶向 TAP 表达或功能以逃避免疫监视，以及一些策略，通过这些策略可以将下调 TAP 的细胞呈递的肽库作为治疗策略，以动员不依赖于 TAP 的 CD8 T 细胞反应。最后，我们讨论 TAP 多态性和 TAP 在遗传性疾病中的作用。
In the late 1980s and early 1990s, the hunt for a transporter molecule ostensibly responsible for the translocation of peptides across the endoplasmic reticulum (ER) membrane yielded the successful discovery of transporter associated with antigen processing (TAP) protein. TAP is a heterodimer complex comprised of TAP1 and TAP2, which utilizes ATP to transport cytosolic peptides into the ER across its membrane. In the ER, together with other components it forms the peptide loading complex (PLC), which directs loading of high affinity peptides onto nascent major histocompatibility complex class I (MHC-I) molecules that are then transported to the cell surface for presentation to CD8+ T cells. TAP also plays a crucial role in transporting peptides into phagosomes and endosomes during cross-presentation in dendritic cells (DCs). Because of the critical role that TAP plays in both classical MHC-I presentation and cross-presentation, its expression and function are often compromised by numerous types of cancers and viruses to evade recognition by cytotoxic CD8 T cells. Here we review the discovery and function of TAP with a major focus on its role in cross-presentation in DCs. We discuss a recently described emergency route of noncanonical cross-presentation that is mobilized in DCs upon TAP blockade to restore CD8 T cell cross-priming. We also discuss the various strategies employed by cancer cells and viruses to target TAP expression or function to evade immunosurveillance - along with some strategies by which the repertoire of peptides presented by cells which downregulate TAP can be targeted as a therapeutic strategy to mobilize a TAP-independent CD8 T cell response. Lastly, we discuss TAP polymorphisms and the role of TAP in inherited disorders.
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DOI：
10.1084/jem.20170229
发表时间：
2017-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Alloatti A;Rookhuizen DC;Joannas L;Carpier JM;Iborra S;Magalhaes JG;Yatim N;Kozik P;Sancho D;Albert ML;Amigorena S
通讯作者：
Amigorena S
影响因子：
4.4
作者：
Ambagala, APN;Hinkley, S;Srikumaran, S
通讯作者：
Srikumaran, S
DOI：
10.1073/pnas.1222342110
发表时间：
2013-02-26
影响因子：
11.1
作者：
Boyle, Louise H.;Hermann, Clemens;Trowsdale, John
通讯作者：
Trowsdale, John
影响因子：
4.4
作者：
Benko, Szilvia;Magalhaes, Joao G.;Girardin, Stephen E.
通讯作者：
Girardin, Stephen E.
影响因子：
30.5
作者：
Barbet G;Nair-Gupta P;Schotsaert M;Yeung ST;Moretti J;Seyffer F;Metreveli G;Gardner T;Choi A;Tortorella D;Tampé R;Khanna KM;García-Sastre A;Blander JM
通讯作者：
Blander JM