Arunachalam B, Pan M, Cresswell P
Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA.
J Immunol. 1998 Jun 15;160(12):5797-806.
The generation of invariant chain-free MHC class II molecules and their association with endocytically generated peptides are thought to occur in specialized lysosome-like compartments called MIICs (MHC class II compartments). A number of in vitro studies have shown that large denatured proteins can bind to class II molecules, and that class II association can protect the bound segment of protein from proteolytic degradation. In this work, we present what we believe is the first example of an intact endogenous protein (IP30) binding in an allele-dependent fashion to class II molecules in vivo. IP30 is an IFN-gamma-inducible 35-kDa glycoprotein that localizes in MIICs. In this study, we show that intact IP30 binds to certain HLA-DR alleles via an N-terminal prosequence. The association takes place in the endocytic pathway following removal of invariant chain from class II molecules and before their cell surface expression. We also show that DR-IP30 complexes are SDS stable. The potential precursor-product relationship between DR-IP30 complexes and the DR-peptide complex is discussed.
无恒定链的MHC II类分子的产生及其与内吞产生的肽的结合被认为发生在称为MIICs（MHC II类区室）的特殊溶酶体样区室中。许多体外研究表明，大的变性蛋白可以与II类分子结合，并且II类分子的结合可以保护蛋白质的结合片段不被蛋白水解降解。在这项工作中，我们展示了我们认为是完整内源性蛋白（IP30）在体内以等位基因依赖性方式与II类分子结合的首个例子。IP30是一种干扰素-γ诱导的35 kDa糖蛋白，定位于MIICs中。在本研究中，我们表明完整IP30通过N端前序列与某些HLA-DR等位基因结合。这种结合发生在内吞途径中，在II类分子的恒定链被去除之后且在其细胞表面表达之前。我们还表明DR-IP30复合物对SDS稳定。讨论了DR-IP30复合物与DR-肽复合物之间潜在的前体-产物关系。
