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通过单个p31和p41亚型在体内重建转基因小鼠中的恒定链功能。

Reconstitution of invariant chain function in transgenic mice in vivo by individual p31 and p41 isoforms.

作者信息

Shachar I, Elliott E A, Chasnoff B, Grewal I S, Flavell R A

机构信息

Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.

出版信息

Immunity. 1995 Sep;3(3):373-83. doi: 10.1016/1074-7613(95)90121-3.

DOI:10.1016/1074-7613(95)90121-3
PMID:7553001
Abstract

MHC class II molecules associate with invariant chain (li) during biosynthesis. If facilitates folding of class II molecules, interferes with their association with peptides, and is involved in their transport. The murine Ii gene encodes two chains, p31 and p41. The role of these isoforms has been studied in vitro only in inappropriate antigen-presenting cells. To circumvent this problem, we have generated invariant chain-deficient mice (delta Ii), which express exclusively the p31 and p41 isoforms. Low level expression of p31 or p41 is not sufficient for rescuing high levels of cell surface class II expression. However, low levels of the typical compact dimer conformation indicative of tight peptide binding are observed. Thus, both isoforms participate in class II folding and assembly. Furthermore, p31 and p41 retrieve the CD4+ T cell population, which is reduced in the (delta Ii) mice. Moreover, the immune response to protein antigen is restored by both isoforms.

摘要

MHC II类分子在生物合成过程中与恒定链(Ii)结合。它促进II类分子的折叠,干扰其与肽的结合,并参与其运输。小鼠Ii基因编码两条链,p31和p41。这些异构体的作用仅在不适当的抗原呈递细胞中进行了体外研究。为了解决这个问题,我们培育出了恒定链缺陷小鼠(ΔIi),其仅表达p31和p41异构体。p31或p41的低水平表达不足以挽救高水平的细胞表面II类分子表达。然而,观察到了低水平的典型紧密二聚体构象,这表明存在紧密的肽结合。因此,两种异构体都参与II类分子的折叠和组装。此外,p31和p41可恢复CD4+ T细胞群体,该群体在(ΔIi)小鼠中减少。此外,两种异构体都能恢复对蛋白质抗原的免疫反应。

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