scholarly journals Accelerated Turnover of MHC Class II Molecules in Nonobese Diabetic Mice Is Developmentally and Environmentally Regulated In Vivo and Dispensable for Autoimmunity

2013 ◽  
Vol 190 (12) ◽  
pp. 5961-5971 ◽  
Author(s):  
Alessandra De Riva ◽  
Mark C. Varley ◽  
Leslie J. Bluck ◽  
Anne Cooke ◽  
Michael J. Deery ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Class Ii ◽  
Diabetic Mice ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice ◽  
Mhc Class Ii Molecules

scholarly journals A Self MHC Class II β-Chain Peptide Prevents Diabetes in Nonobese Diabetic Mice

2000 ◽  
Vol 164 (12) ◽  
pp. 6610-6620 ◽  
Author(s):  
Pratibha Chaturvedi ◽  
Babita Agrawal ◽  
Marc Zechel ◽  
Edwin Lee-Chan ◽  
Bhagirath Singh
Keyword(s):  
Mhc Class Ii ◽  
Class Ii ◽  
Diabetic Mice ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice ◽  
Β Chain

Effect of MHC Class II Encoding Transgenes on Autoimmunity in Nonobese Diabetic Mice

1994 ◽  
pp. 183-190
Author(s):  
Anne Cooke ◽  
Lorraine A. O'Reilly ◽  
Alan G. Baxter ◽  
Patricia Ozegbe ◽  
Patricia R. Hutchings ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Class Ii ◽  
Diabetic Mice ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice

scholarly journals Early Endosomes Are Required for Major Histocompatiblity Complex Class II Transport to Peptide-loading Compartments

1999 ◽  
Vol 10 (9) ◽  
pp. 2891-2904 ◽  
Author(s):  
Valérie Brachet ◽  
Gérard Péhau-Arnaudet ◽  
Catherine Desaymard ◽  
Graça Raposo ◽  
Sebastian Amigorena
Keyword(s):  
Mhc Class Ii ◽  
Class Ii ◽  
Endocytic Pathway ◽  
Cross Linking ◽  
Histocompatibility Complex ◽  
Early Endosomes ◽  
Peptide Loading ◽  
Golgi Network ◽  
Mhc Class Ii Molecules

Antigen presentation to CD4+ T lymphocytes requires transport of newly synthesized major histocompatibility complex (MHC) class II molecules to the endocytic pathway, where peptide loading occurs. This step is mediated by a signal located in the cytoplasmic tail of the MHC class II-associated Ii chain, which directs the MHC class II-Ii complexes from the trans-Golgi network (TGN) to endosomes. The subcellular machinery responsible for the specific targeting of MHC class II molecules to the endocytic pathway, as well as the first compartments these molecules enter after exit from the TGN, remain unclear. We have designed an original experimental approach to selectively analyze this step of MHC class II transport. Newly synthesized MHC class II molecules were caused to accumulate in the Golgi apparatus and TGN by incubating the cells at 19°C, and early endosomes were functionally inactivated by in vivo cross-linking of transferrin (Tf) receptor–containing endosomes using Tf-HRP complexes and the HRP-insoluble substrate diaminobenzidine. Inactivation of Tf-containing endosomes caused a marked delay in Ii chain degradation, peptide loading, and MHC class II transport to the cell surface. Thus, early endosomes appear to be required for delivery of MHC class II molecules to the endocytic pathway. Under cross-linking conditions, most αβIi complexes accumulated in tubules and vesicles devoid of γ-adaptin and/or mannose-6-phosphate receptor, suggesting an AP1-independent pathway for the delivery of newly synthesized MHC class II molecules from the TGN to endosomes.

scholarly journals In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes

2000 ◽  
Vol 191 (1) ◽  
pp. 97-104 ◽  
Author(s):  
Li Wen ◽  
F. Susan Wong ◽  
Jie Tang ◽  
Ning-Yuan Chen ◽  
Martha Altieri ◽  
...  
Keyword(s):  
T Cells ◽  
Transgenic Mice ◽  
Mhc Class Ii ◽  
Spontaneous Diabetes ◽  
Class Ii ◽  
Β Cells ◽  
Leukocyte Antigen ◽  
Hla Dqa1 ◽  
Mhc Class Ii Molecules

Although DQA1*0301/DQB1*0302 is the human histocompatibility leukocyte antigen (HLA) class II gene most commonly associated with human type 1 diabetes, direct in vivo experimental evidence for its diabetogenic role is lacking. Therefore, we generated C57BL/6 transgenic mice that bear this molecule and do not express mouse major histocompatibility complex (MHC) class II molecules (DQ8+/mII−). They did not develop insulitis or spontaneous diabetes. However, when DQ8+/mII− mice were bred with C57BL/6 mice expressing costimulatory molecule B7-1 on β cells (which normally do not develop diabetes), 81% of the DQ8+/mII−/B7-1+ mice developed spontaneous diabetes. The diabetes was accompanied by severe insulitis composed of both T cells (CD4+ and CD8+) and B cells. T cells from the diabetic mice secreted large amounts of interferon γ, but not interleukin 4, in response to DQ8+ islets and the putative islet autoantigens, insulin and glutamic acid decarboxylase (GAD). Diabetes could also be adoptively transferred to irradiated nondiabetic DQ8+/mII−/B7-1+ mice. In striking contrast, none of the transgenic mice in which the diabetes protective allele (DQA1*0103/DQB1*0601, DQ6 for short) was substituted for mouse MHC class II molecules but remained for the expression of B7-1 on pancreatic β cells (DQ6+/mII−/B7-1+) developed diabetes. Only 7% of DQ−/mII−/B7-1+ mice developed diabetes at an older age, and none of the DQ−/mII+/B7-1+ mice or DQ8+/mII+/B7-1+ mice developed diabetes. In conclusion, substitution of HLA-DQA1*0301/DQB1*0302, but not HLA-DQA1*0103/DQB1*0601, for murine MHC class II provokes autoimmune diabetes in non–diabetes-prone rat insulin promoter (RIP).B7-1 C57BL/6 mice. Our data provide direct in vivo evidence for the diabetogenic effect of this human MHC class II molecule and a unique “humanized” animal model of spontaneous diabetes.

scholarly journals Mapping Non-Class II H2-Linked Loci for Type 1 Diabetes in Nonobese Diabetic Mice

Diabetes ◽  
2004 ◽  
Vol 53 (12) ◽  
pp. 3323-3327 ◽  
Author(s):  
N. Deruytter ◽  
O. Boulard ◽  
H.-J. Garchon
Keyword(s):  
Type 1 Diabetes ◽  
Class Ii ◽  
Diabetic Mice ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice
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