The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice.
The spontaneous destruction of insulin producing pancreatic beta cells in non-obese diabetic (NOD) mice provides a valuable model of type 1 diabetes. As in humans, disease susceptibility is controlled by the classical MHC class II genes that guide CD4(+) T cell responses to self and foreign antigens...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0056738&type=printable |
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| author | Marc A J Morgan Pari S S Muller Arne Mould Stephen A Newland Jennifer Nichols Elizabeth J Robertson Anne Cooke Elizabeth K Bikoff |
| author_facet | Marc A J Morgan Pari S S Muller Arne Mould Stephen A Newland Jennifer Nichols Elizabeth J Robertson Anne Cooke Elizabeth K Bikoff |
| author_sort | Marc A J Morgan |
| collection | DOAJ |
| description | The spontaneous destruction of insulin producing pancreatic beta cells in non-obese diabetic (NOD) mice provides a valuable model of type 1 diabetes. As in humans, disease susceptibility is controlled by the classical MHC class II genes that guide CD4(+) T cell responses to self and foreign antigens. It has long been suspected that the dedicated class II chaperone designated HLA-DM in humans or H-2M in mice also makes an important contribution, but due to tight linkage within the MHC, a possible role played by DM peptide editing has not been previously tested by conventional genetic approaches. Here we exploited newly established germ-line competent NOD ES cells to engineer a loss of function allele. DM deficient NOD mice display defective class II peptide occupancy and surface expression, and are completely protected against type 1 diabetes. Interestingly the mutation results in increased proportional representation of CD4(+)Foxp3(+) regulatory T cells and the absence of pathogenic CD4(+) T effectors. Overall, this striking phenotype establishes that DM-mediated peptide selection plays an essential role in the development of autoimmune diabetes in NOD mice. |
| format | Article |
| id | doaj-art-7eebef782171470eb7208f3e17de928d |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-7eebef782171470eb7208f3e17de928d2025-08-20T02:30:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5673810.1371/journal.pone.0056738The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice.Marc A J MorganPari S S MullerArne MouldStephen A NewlandJennifer NicholsElizabeth J RobertsonAnne CookeElizabeth K BikoffThe spontaneous destruction of insulin producing pancreatic beta cells in non-obese diabetic (NOD) mice provides a valuable model of type 1 diabetes. As in humans, disease susceptibility is controlled by the classical MHC class II genes that guide CD4(+) T cell responses to self and foreign antigens. It has long been suspected that the dedicated class II chaperone designated HLA-DM in humans or H-2M in mice also makes an important contribution, but due to tight linkage within the MHC, a possible role played by DM peptide editing has not been previously tested by conventional genetic approaches. Here we exploited newly established germ-line competent NOD ES cells to engineer a loss of function allele. DM deficient NOD mice display defective class II peptide occupancy and surface expression, and are completely protected against type 1 diabetes. Interestingly the mutation results in increased proportional representation of CD4(+)Foxp3(+) regulatory T cells and the absence of pathogenic CD4(+) T effectors. Overall, this striking phenotype establishes that DM-mediated peptide selection plays an essential role in the development of autoimmune diabetes in NOD mice.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0056738&type=printable |
| spellingShingle | Marc A J Morgan Pari S S Muller Arne Mould Stephen A Newland Jennifer Nichols Elizabeth J Robertson Anne Cooke Elizabeth K Bikoff The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice. PLoS ONE |
| title | The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice. |
| title_full | The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice. |
| title_fullStr | The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice. |
| title_full_unstemmed | The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice. |
| title_short | The nonconventional MHC class II molecule DM governs diabetes susceptibility in NOD mice. |
| title_sort | nonconventional mhc class ii molecule dm governs diabetes susceptibility in nod mice |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0056738&type=printable |
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