Susceptibility to HLA-DM Protein is Determined by a Dynamic Conformation of Major Histocompatibility Complex Class II Molecule Bound with Peptide

Yin L, et al., 289(34):23449-64, J Biol Chem, 2014

These authors investigated the sequence and structural determinants of human leukocyte antigen DM (HLA-DM) interaction. HLA-DM arbitrates the exchange of peptides loaded onto major histocompatibility complex class II (MHCII) molecules during antigen presentation. These molecules typically found on antigen-presenting cells such as the B cells, dendritic cells, endothelial cells, and phagocytes. Non-optimal peptide interactions often lead to low MHCII binding affinities and hence kinetic instability. These peptides are inclined to HLA-DM-mediated peptide exchange. The biochemical and biophysical approaches used in this investigation helped to identify changes that are often accompanying a conformational alteration. The binding studies involved assays from both Biacore and Pall ForteBio Octet systems. Binding of the wild type or mutant HLA-DM to immobilized HLA-DO (DM negative regulator) were performed on an Octet system.

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