Distinct antigen MHC class II complexes generated by separate processing pathways
Distinct antigen MHC class II complexes generated by separate processing pathways
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DOI：
10.1002/j.1460-2075.1996.tb01083.x
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发表时间：
1996-12-16
期刊：
影响因子：
11.4
通讯作者：
Unanue, ER
中科院分区：
文献类型：
--
作者：
Lindner, R;Unanue, ER
MHC II 类分子的肽结合位点在两端开放，因此不限制结合配体的长度。在此，我们证明部分折叠的蛋白抗原 (*HEL) 与纯化的 MHC II 类分子 I-A(k) (A(k)) 自发形成 SDS 不稳定复合物。这些复合物也在抗原呈递细胞 (APC) 的表面上被检测到，它们刺激了 T 细胞，但是，它们在内吞作用后迅速消失，*HEL 的细胞内加工产生了 SDS 稳定、长寿命的 A(k) 复合物，其中含有 *HEL 肽和出人意料的全长 *HEL。两种 SDS 稳定的产物都是在低 pH 区室中形成，然后转运到质膜，在 与 *HEL 肽相反，*HEL 的稳定结合发生在需要成熟 II 类分子且不涉及 HLA-DM 或蛋白酶的替代途径中，SDS 稳定的 *HEL-A(k) 复合物是通过内体 A(k) 与内吞的 *HEL 反应形成的，而不是通过直接转化源自质膜的 SDS 不稳定复合物。 两种 MHC II 类加载途径之间的根本区别，并首次证明全长蛋白质是抗原加工的产物。
The peptide binding site of MHC class II molecules is open at both ends and, therefore, does not restrict the length of the bound ligand, Here we show that a partially folded protein antigen (*HEL) spontaneously formed SDS-unstable complexes with the purified MHC class II molecule I-A(k) (A(k)). These complexes were also detected on the surface of antigen-presenting cells (APCs) where they stimulated T cells, However, they rapidly disappeared after endocytosis, Intracellular processing of *HEL gave rise to SDS-stable, long-lived A(k) complexes containing *HEL peptides and, unexpectedly, full-length *HEL, Both SDS-stable products were formed in low pH compartments and then transported to the plasma membrane, In contrast to *HEL peptides, the stable association of *HEL occurred in an alternative pathway that required mature class II molecules and did not involve HLA-DM or proteases, SDS-stable *HEL-A(k) complexes were formed by a reaction of endosomal A(k) with endocytosed *HEL, but not by direct conversion of SDS-unstable complexes derived from the plasma membrane, Our work establishes a fundamental difference between the two MHC class II loading pathways and for the first time demonstrates a full-length protein as a product of antigen processing.