Proteasomes, TAP, and endoplasmic reticulum-associated aminopeptidase associated with antigen processing control CD4+ Th cell responses by regulating indirect presentation of MHC class II-restricted cytoplasmic antigens.
Proteasomes, TAP, and endoplasmic reticulum-associated aminopeptidase associated with antigen processing control CD4+ Th cell responses by regulating indirect presentation of MHC class II-restricted cytoplasmic antigens.
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DOI：
10.4049/jimmunol.1100525
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发表时间：
2011-06-15
期刊：
影响因子：
--
通讯作者：
Joyce S
中科院分区：
文献类型：
--
作者：
Dragovic SM;Hill T;Christianson GJ;Kim S;Elliott T;Scott D;Roopenian DC;Van Kaer L;Joyce S
来自病毒、胞质细菌、肿瘤和同种异体移植物的胞质Ag通过MHC I类或II类分子呈递给T细胞。在II类限制性Ag的情况下，专职Ag呈递细胞在摄取死亡的II类阴性细胞期间获得它们，并通过称为间接呈递的过程呈递它们。一般认为，胞质银加工机，它提供的肽介绍由I类分子，发挥非常小的作用，间接介绍II类限制，胞质Ag。值得注意的是，在测试这一假设时，我们发现，蛋白酶体，TAP和ERAAP，但不是tapasin，部分破坏或去除细胞质，II类限制性Ag，使它们的抑制或缺陷导致显着增加的TH细胞对同种异体移植物（HY）和微生物（李斯特菌）Ag的反应，这两者都是间接提出的。这种效应既不是由于增强ER相关的降解，也不是由于I类和II类分子之间对Ag的竞争。从这些研究结果中出现了一种新的模型，其中胞质银加工机械调节可用于介绍II类分子的细胞质肽的数量，因此调节TH细胞的反应。
Cytoplasmic Ags derived from viruses, cytosolic bacteria, tumours and allografts are presented to T cells by MHC class I or class II molecules. In the case of class II-restricted Ags, professional Ag-presenting cells acquire them during uptake of dead, class II-negative cells and present them via a process called indirect presentation. It is generally assumed that the cytosolic Ag-processing machinery—which supplies peptides for presentation by class I molecules—plays very little role in indirect presentation of class II-restricted, cytoplasmic Ags. Remarkably, upon testing this assumption, we found that proteasomes, TAP and ERAAP, but not tapasin, partially destroyed or removed cytoplasmic, class II-restricted Ags such that their inhibition or deficiency led to dramatically increased TH cell responses to allograft (HY) and microbial (Listeria monocytogenes) Ags, both of which are indirectly presented. This effect was neither due to enhanced ER-associated degradation nor competition for Ag between class I and class II molecules. From these findings a novel model emerges in which the cytosolic Ag-processing machinery regulates the quantity of cytoplasmic peptides available for presentation by class II molecules, and hence modulates TH cell responses.
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影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
影响因子：
4.8
作者：
Kroeger, Heike;Miranda, Elena;Lomas, David A.
通讯作者：
Lomas, David A.
影响因子：
4
作者：
Dani, A;Chaudhry, A;Mayor, S
通讯作者：
Mayor, S
影响因子：
32.4
作者：
Aoshi, Taiki;Zinselmeyer, Bernd H.;Miller, Mark J.
通讯作者：
Miller, Mark J.
DOI：
10.1073/pnas.88.8.3290
发表时间：
1991-04-01
影响因子：
11.1
作者：
BROOKS, A;HARTLEY, S;MCCLUSKEY, J
通讯作者：
MCCLUSKEY, J