A general model of invariant chain association with class II major histocompatibility complex proteins

C. Lee, H. M. McConnell
1995 Proceedings of the National Academy of Sciences of the United States of America  
The binding of invariant chain to major histocompatibility complex (MHC) proteins is an important step in processing of MHC class II proteins and in antigen presentation. The question of how invariant chain can bind to all MHC class II proteins is central to understanding these processes. We have employed molecular modeling to predict the structure of class 11-associated invariant chain peptide (CLIP)-MHC protein complexes and to ask whether the predicted mode of association could be general
more » ... oss all MHC class II proteins. CLIP fits identically into the MHC class II alleles HLA-DR3, I-Ak, I-Au, and I-Ad, with a consistent pattern of hydrogen bonds, contacts, and hydrophobic burial and without bad contacts. Our model predicts the burial of CLIP residues in the deep P1 and P9 anchor pockets and other detailed interactions, which we have compared with available data. The predicted pattern of I-A allele-specific effects on CLIP binding is very similar to that observed experimentally by alanine-scanning mutations of CLIP. Together, these results indicate that CLIP may bind in a single, general way across products of MHC class II alleles.
doi:10.1073/pnas.92.18.8269 pmid:7667280 pmcid:PMC41138 fatcat:ahyc6nt7bzcolgm2v6mqb2jl44