Hla-Dm Recognizes the Flexible Conformation of Major Histocompatibility Complex Class II

作者：Chih-Ling Chou, Scheherazade Sadegh‐Nasseri · 发表于：The Journal of Experimental Medicine · 年份：2000 · DOI：10.1084/jem.192.12.1697 · 被引用次数：123 · 研究领域：Immunotherapy and Immune Responses、T-cell and B-cell Immunology、Immune Cell Function and Interaction

DM facilitates formation of high affinity complexes of peptide-major histocompatibility complex (MHC) by release of class II MHC-associated invariant chain peptide (CLIP). This has been proposed to occur through discrimination of complex stability. By probing kinetic and conformational intermediates of the wild-type and mutant human histocompatibility leukocyte antigen (HLA)-DR1-peptide complexes, and examining their reactivities with DM, we propose that DM interacts with the flexible hydrophobic pocket 1 of DR1 and converts the molecule into a conformation that is highly peptide receptive. A more rigid conformation, generated upon filling of pocket 1, is less susceptible to DM effects. Thus, DM edits peptide-MHC by recognition of the flexibility rather than stability of the complex.