Cutting Edge: HLA-DM Functions through a Mechanism That Does Not Require Specific Conserved Hydrogen Bonds in Class II MHC-Peptide Complexes
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- Zemin Zhou
- *Department of Pathology, University of Utah, Salt Lake City, UT 84112;
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- Kari A. Callaway
- *Department of Pathology, University of Utah, Salt Lake City, UT 84112;
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- Dominique A. Weber
- †Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322;
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- Peter E. Jensen
- *Department of Pathology, University of Utah, Salt Lake City, UT 84112;
説明
<jats:title>Abstract</jats:title> <jats:p>HLA-DM catalyzes peptide dissociation and exchange in class II MHC molecules through a mechanism that has been proposed to involve the disruption of specific components of the conserved hydrogen bond network in MHC-peptide complexes. HLA-DR1 molecules with alanine substitutions at each of the six conserved H- bonding positions were expressed in cells, and susceptibility to DM catalytic activity was evaluated by measuring the release of CLIP. The mutants αN62A, αN69A, αR76A, and βH81A DR1 were fully susceptible to DM-mediated CLIP release, and βN82A resulted in spontaneous release of CLIP. Using recombinant soluble DR1 molecules, the amino acid βN82 was observed to contribute disproportionately in stabilizing peptide complexes. Remarkably, the catalytic potency of DM with each β-chain mutant was equal to or greater than that observed with wild-type DR1. Our results support the conclusion that no individual component of the conserved hydrogen bond network plays an essential role in the DM catalytic mechanism.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 183 (7), 4187-4191, 2009-10-01
The American Association of Immunologists