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- Title
I-Ag7 is subject to post-translational chaperoning by CLIP.
- Authors
Rinderknecht, Cornelia H.; Ning Lu; Crespo, Oliver; Phi Truong; Tieying Hou; Nan Wang; Rajasekaran, Narendiran; Mellins, Elizabeth D.
- 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.
- Subjects
MAJOR histocompatibility complex; AUTOIMMUNE diseases; PEPTIDES; ANTIGENS; ENDOPLASMIC reticulum
- Publication
International Immunology, 2010, Vol 22, Issue 8, p705
- ISSN
0953-8178
- Publication type
Article
- DOI
10.1093/intimm/dxq056