Invariant chain dissociation from class II MHC is a catalyst for foreign peptide binding.
Invariant chain dissociation from class II MHC is a catalyst for foreign peptide binding.
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II 类 MHC 的不变链解离是外源肽结合的催化剂。
DOI：
10.1111/j.1749-6632.1994.tb44285.x
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发表时间：
1994
影响因子：
5.2
通讯作者：
Humphreys,RE
中科院分区：
文献类型：
--
作者：
Reyes,VE;Daibata,M;Espejo,R;Humphreys,RE
I1类MHC相关不变链（li）作为伴侣分子，促进I1类MHC分子在内质网中的转运和组装，并将其分选至含有内吞抗原的区室。由于它们与I1、I1类MHC α p链的结合，它们不结合ER中自身的内源性肽。II类MHC-Ii复合物移动通过高尔基体并最终进入内吞途径。在I1类MHC离开细胞表面之前，I1类MHC-li复合物在内体隔室中停留2-3小时。而在核内体中，I 1类MHC通过组织蛋白酶B作用于IL 2而游离出IL 2。这种解离事件允许I 1类MHC结合肽，变得稳定，并排出到质膜。我们的研究表明，T细胞呈递的肽与I1类MHC的结合是与组织蛋白酶B释放li同时发生的过程。另一种内体蛋白酶，组织蛋白酶D，切割，但不释放锂，不增强肽结合。然而，在存在组织蛋白酶B的情况下，痕量水平的组织蛋白酶D进一步增强了I1类MHC对肽的结合。我们决定检测在li释放过程中形成的I1类构象中间体是否比I1类MHC-1更有效地结合肽。U复合物或I1类MHC自由基。我们用放射性标记的HLA-DR-1-限制性流感病毒MA（18-29）肽孵育来自HLA-DR-1 ′细胞系（JESTHOM）的溶解微粒体膜，该肽与异双功能交联剂（HSAB）偶联。在不同浓度的组织蛋白酶B存在下，在pH 5下孵育不同的时间段，所述组织蛋白酶B从I1类裂解并释放li
The class I1 MHC-associated invariant chain (li) acts as a chaperone in facilitating the transport and assembly of class I1 MHC molecules in the endoplasmic reticulum and their sorting to compartments containing endocytosed antigens. As a result of their association with li, class I1 MHC ap chains do not bind self, endogenous peptides resident in the ER.'Class I1 MHC-li complexes move through the Golgi apparatus and eventually enter the endocytic pathway. Class I1 MHC-li complexes reside in endosomal compartments for 2-3 hours prior to the exit of class I1 MHC to the cell surface. While in endosomes, class I1 MHC become free of li through the action of cathepsin B on lL2 This dissociation event permits class I1 MHC to bind peptides, become stable, and egress to the plasma membrat~ e.~ Our studies demonstrate that the binding of T-cell-presented peptides to class I1 MHC occurs as a concurrent process with the release of li by cathepsin B. Another endosomal protease, cathepsin D, which cleaved but did not release li, did not enhance peptide binding. However, trace levels of cathepsin D in the presence of cathepsin B further enhanced peptide binding by class I1 MHC.Because peptide binding to affinity-purified class I1 MHC is very slow, relative to the time required for peptide binding by living cells, we decided to examine whether a class I1 conformational intermediate formed during the release of li is more efficient in binding peptides than is either class I1 MHC-U complexes or lifreed class I1 MHC. We incubated solubilized microsomal membranes from an HLADR-1'cell line (JESTHOM) with a radiolabeled, HLA-DR-1-restricted influenza virus MA (18-29) peptide which was coupled to a heterobifunctional cross-linker (HSAB). Incubations were done at pH 5 for various time periods in the presence of varying concentrations of cathepsin B, which cleaves and releases li from class I1