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I-Ag7 is subject to post-translational chaperoning by CLIP

By Cornelia H. Rinderknecht, Ning Lu, Oliver Crespo, Phi Truong, Tieying Hou, Nan Wang, Narendiran Rajasekaran and Elizabeth D. Mellins

Abstract

Several MHC class II alleles linked with autoimmune diseases form unusually low-stability complexes with class II-associated invariant chain peptides (CLIP), leading us to hypothesize that this is an important feature contributing to autoimmune pathogenesis. We recently demonstrated a novel post-endoplasmic reticulum (ER) chaperoning role of the CLIP peptides for the murine class II allele I-Ed. In the current study, we tested the generality of this CLIP chaperone function using a series of invariant chain (Ii) mutants designed to have varying CLIP affinity for I-Ag7. In cells expressing these Ii CLIP mutants, I-Ag7 abundance, turnover and antigen presentation are all subject to regulation by CLIP affinity, similar to I-Ed. However, I-Ag7 undergoes much greater quantitative changes than observed for I-Ed. In addition, we find that Ii with a CLIP region optimized for I-Ag7 binding may be preferentially assembled with I-Ag7 even in the presence of higher levels of wild-type Ii. This finding indicates that, although other regions of Ii interact with class II, CLIP binding to the groove is likely to be a dominant event in assembly of nascent class II molecules with Ii in the ER

Topics: Original Research Papers
Publisher: Oxford University Press
OAI identifier: oai:pubmedcentral.nih.gov:2908477
Provided by: PubMed Central
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