HLA-DM recognizes the flexible conformation of major histocompatibility complex class II.
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.
Chou
C L
CL
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Sadegh-Nasseri
S
S
D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011994:Recombinant Proteins; C045084:invariant chain; D014364:Tryptophan