Evidence for a human leucocyte antigen-DM-induced structural change in human leucocyte antigen-DOβ

Francis Deshaies, Djibril A. Diallo, Jean Simon Fortin, Helen M. O'Rourke, Abdul Mohammad Pezeshki, Angélique Bellemare-Pelletier, Nicola Raby, Nathalie Bédard, Alexandre Brunet, Lisa K. Denzin, Jacques Thibodeau

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Summary Human leucocyte antigen (HLA)-DO is a non-classical major histocompatibility complex class II molecule which modulates the function of HLA-DM and the loading of antigenic peptides on molecules such as HLA-DR. The bulk of HLA-DO associates with HLA-DM and this interaction is critical for HLA-DO egress from the endoplasmic reticulum. HLA-DM assists the early steps of HLA-DO maturation presumably through the stabilization of the interactions between the N-terminal regions of the α and β chains. To evaluate a possible role for HLA-DM in influencing the conformation of HLA-DO, we made use of a monoclonal antibody, Mags.DO5, that was raised against HLA-DO/DM complexes. Using transfected cells expressing mismatched heterodimers between HLA-DR and -DO chains, we found that the epitope for Mags.DO5 is located on the DOβ chain and that Mags.DO5 reactivity was increased upon cotransfection with HLA-DM. Our results suggest that HLA-DM influences the folding of HLA-DO in the endoplasmic reticulum. A mutant HLA-DO showing reduced capacity for endoplasmic reticulum egress was better recognized by Mags.DO5 in the presence of HLA-DM. On the other hand, an HLA-DO mutant capable of endoplasmic reticulum egress on its own was efficiently recognized by Mags.DO5, irrespective of the presence of HLA-DM. Taken together, our results suggest that HLA-DM acts as a private chaperone, directly assisting the folding of HLA-DO to promote egress from the endoplasmic reticulum.

Original languageEnglish (US)
Pages (from-to)408-417
Number of pages10
JournalImmunology
Volume127
Issue number3
DOIs
StatePublished - Jul 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

  • Antigen presentation
  • Antigen processing
  • B cells
  • Human
  • Major histocompatibility complex

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