Stable surface expression of invariant chain prevents peptide presentation by HLA‐DR.
Stable surface expression of invariant chain prevents peptide presentation by HLA‐DR.
复制标题
不变链的稳定表面表达可防止 HLA-DR 的肽呈递。
DOI：
10.1002/j.1460-2075.1992.tb05351.x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Eric O Long
中科院分区：
文献类型：
--
作者：
P. Roche;C. L. Teletski;D. Karp;V. Pinet;O. Bakke;Eric O Long
II类主要组织相容性复合体（MHC）分子是结合并呈递免疫原性肽至T细胞的细胞表面糖蛋白。在细胞内，II类分子与称为不变（Ii）链的多肽缔合。在成熟II类α β异二聚体的细胞表面表达之前，Ii被蛋白水解降解并从II类复合物解离。使用转染HLA-DR 1和Ii cDNA的人成纤维细胞，我们现在证明，截短Ii的胞质结构域导致Ii无法从α β Ii复合物中解离，并导致II类α β Ii复合物在细胞表面稳定表达。此外，生物化学分析和肽呈递测定表明，具有稳定表面α β Ii复合物的转染子在表面表达非常少的游离α β异二聚体，并且它们向T细胞呈递免疫原性肽的能力非常低效。这些结果支持Ii的胞质结构域负责α β Ii的内体靶向的假设，并直接证明与Ii的缔合干扰II类分子的抗原呈递功能。
Class II major histocompatibility complex (MHC) molecules are cell surface glycoproteins that bind and present immunogenic peptides to T cells. Intracellularly, class II molecules associate with a polypeptide referred to as the invariant (Ii) chain. Ii is proteolytically degraded and dissociates from the class II complex prior to cell surface expression of the mature class II alpha beta heterodimer. Using human fibroblasts transfected with HLA‐DR1 and Ii cDNAs, we now demonstrate that truncation of the cytoplasmic domain of Ii results in the failure of Ii to dissociate from the alpha beta Ii complex and leads to stable expression of class II alpha beta Ii complexes on the cell surface. Furthermore, biochemical analysis and peptide presentation assays demonstrated that transfectants with stable surface alpha beta Ii complexes expressed very few free alpha beta heterodimers at the surface and were very inefficient in their ability to present immunogenic peptides to T cells. These results support the hypothesis that the cytoplasmic domain of Ii is responsible for endosomal targeting of alpha beta Ii and directly demonstrate that association with Ii interferes with the antigen presentation function of class II molecules.