Abstract
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 DR 1 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.
Original language | English (US) |
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Pages (from-to) | 1697-1706 |
Number of pages | 10 |
Journal | Journal of Experimental Medicine |
Volume | 192 |
Issue number | 12 |
DOIs | |
State | Published - Dec 18 2000 |
Keywords
- Antigen processing
- Fluorometry
- HLA-DR antigens
- Molecular conformation
- Surface plasmon resonance
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology