Mechanisms of peptide repertoire selection by HLA-DM

• Autores: Wouter Pos, Dhruv K. Sethi, Kai W. Wucherpfennig
• Localización: Trends in immunology, ISSN 1471-4906, Vol. 34, Nº. 10, 2013, págs. 495-501
• Idioma: inglés
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• Resumen

  • Recently, crystal structures of key complexes in antigen presentation have been reported. HLA-DM functions in antigen presentation by catalyzing dissociation of an invariant chain remnant from the peptide binding groove and stabilizing empty MHC class II proteins in a peptide-receptive conformation. The crystal structure of a MHC class II�HLA-DM complex explains how HLA-DM stabilizes an otherwise short-lived transition state and promotes a rapid peptide exchange process that favors the highest-affinity ligands. HLA-DO has sequence similarity with MHC class II molecules yet inhibits antigen presentation. The structure of the HLA-DO�HLA-DM complex shows that it blocks HLA-DM activity as a substrate mimic. Alterations in the efficiency of DM-mediated peptide selection may contribute to autoimmune pathologies, which will be an exciting area for future investigation.