PMID- 20547545 OWN - NLM STAT- MEDLINE DCOM- 20101123 LR - 20211020 IS - 1460-2377 (Electronic) IS - 0953-8178 (Print) IS - 0953-8178 (Linking) VI - 22 IP - 8 DP - 2010 Aug TI - I-Ag7 is subject to post-translational chaperoning by CLIP. PG - 705-16 LID - 10.1093/intimm/dxq056 [doi] AB - 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-E(d). 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-A(g7). In cells expressing these Ii CLIP mutants, I-A(g7) abundance, turnover and antigen presentation are all subject to regulation by CLIP affinity, similar to I-E(d). However, I-A(g7) undergoes much greater quantitative changes than observed for I-E(d). In addition, we find that Ii with a CLIP region optimized for I-A(g7) binding may be preferentially assembled with I-A(g7) 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. FAU - Rinderknecht, Cornelia H AU - Rinderknecht CH AD - Program in Immunology, Stanford University, Stanford, CA 94305, USA. FAU - Lu, Ning AU - Lu N FAU - Crespo, Oliver AU - Crespo O FAU - Truong, Phi AU - Truong P FAU - Hou, Tieying AU - Hou T FAU - Wang, Nan AU - Wang N FAU - Rajasekaran, Narendiran AU - Rajasekaran N FAU - Mellins, Elizabeth D AU - Mellins ED LA - eng GR - T32 AI007290/AI/NIAID NIH HHS/United States GR - T32 AI07290/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20100613 PL - England TA - Int Immunol JT - International immunology JID - 8916182 RN - 0 (Antigens, Differentiation, B-Lymphocyte) RN - 0 (Antigens, Surface) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (I-A g7 antigen) RN - 0 (Molecular Chaperones) RN - 0 (invariant chain) SB - IM MH - Animals MH - Antigens, Differentiation, B-Lymphocyte/genetics/*immunology MH - Antigens, Surface/genetics/immunology MH - B-Lymphocytes/immunology MH - Cell Line, Tumor MH - Flow Cytometry MH - Histocompatibility Antigens Class II/genetics/*immunology MH - Immunoblotting MH - Mice MH - Mice, Inbred BALB C MH - Molecular Chaperones/*immunology MH - Mutation MH - Protein Processing, Post-Translational/*immunology PMC - PMC2908477 EDAT- 2010/06/16 06:00 MHDA- 2010/12/14 06:00 PMCR- 2011/08/01 CRDT- 2010/06/16 06:00 PHST- 2010/06/16 06:00 [entrez] PHST- 2010/06/16 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] PHST- 2011/08/01 00:00 [pmc-release] AID - dxq056 [pii] AID - 10.1093/intimm/dxq056 [doi] PST - ppublish SO - Int Immunol. 2010 Aug;22(8):705-16. doi: 10.1093/intimm/dxq056. Epub 2010 Jun 13.