Evidence for a human leucocyte antigen-DM-induced structural change in human leucocyte antigen-DOβ
| Autor: | Lisa K. Denzin, Helen M. O’Rourke, Nicola Raby, Nathalie Bédard, Angelique Bellemare-Pelletier, Djibril A. Diallo, Jacques Thibodeau, Jean-Simon Fortin, Francis Deshaies, Abdul Mohammad Pezeshki, Alexandre Brunet |
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| Rok vydání: | 2009 |
| Předmět: |
Antigen Presentation
B-Lymphocytes HLA-D Antigens Protein Folding biology Antigen processing Endoplasmic reticulum Immunology Antigen presentation Antibodies Monoclonal STIM1 Original Articles Human leukocyte antigen Endoplasmic Reticulum Transfection Major histocompatibility complex Virology Epitope Cell biology Chaperone (protein) biology.protein Epitopes B-Lymphocyte Humans Immunology and Allergy HeLa Cells |
| Zdroj: | Immunology. 127:408-417 |
| ISSN: | 1365-2567 0019-2805 |
| DOI: | 10.1111/j.1365-2567.2008.02984.x |
| Popis: | 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 alpha and beta 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 DObeta 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. |
| Databáze: | OpenAIRE |
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