| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Diabetes Center, Department of Medicine,
Division of Endocrinology and Metabolism, Department of Veterans Affairs Medical Center, and
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143;
Department of Microbiology and Immunology, Stanford University, Palo Alto, CA 94305; and
¶ Institut National de la Santé et de la Recherche Médicale, Laennec Faculty of Medicine, University of Lyon, Lyon, France
Type 1 diabetes is a T cell-mediated disease in which B cells serve critical Ag-presenting functions. In >95% of type 1 diabetic patients the B cell response to the glutamic acid decarboxylase 65 (GAD65) autoantigen is exclusively directed at conformational epitopes residing on the surface of the native molecule. We have examined how the epitope specificity of Ag-presenting autoimmune B cell lines, derived from a type 1 diabetic patient, affects the repertoire of peptides presented to DRB1*0401-restricted T cell hybridomas. The general effect of GAD65-specific B cells was to enhance Ag capture and therefore Ag presentation. The enhancing effect was, however, restricted to T cell determinants located outside the B cell epitope region, because processing/presentation of T cell epitopes located within the autoimmune B cell epitope were suppressed in a dominant fashion. A similar effect was observed when soluble Abs formed immune complexes with GAD65 before uptake and processing by splenocytes. Thus, GAD65-specific B cells and the Abs they secrete appear to modulate the autoimmune T cell repertoire by down-regulating T cell epitopes in an immunodominant area while boosting epitopes in distant or cryptic regions.
This article has been cited by other articles:
|
|
 |
|
  G. Fenalti, C. S. Hampe, Y. Arafat, R. H.P. Law, J. P. Banga, I. R. Mackay, J. C. Whisstock, A. M. Buckle, and M. J. Rowley COOH-Terminal Clustering of Autoantibody and T-Cell Determinants on the Structure of GAD65 Provide Insights Into the Molecular Basis of Autoreactivity Diabetes, May 1, 2008; 57(5): 1293 - 1301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Oak, L. K. Gilliam, M. Landin-Olsson, C. Torn, I. Kockum, C. R. Pennington, M. J. Rowley, M. R. Christie, J. P. Banga, and C. S. Hampe The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes PNAS, April 8, 2008; 105(14): 5471 - 5476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Shah, A. Tramontano, and S. P. Makker Intramolecular Epitope Spreading in Heymann Nephritis J. Am. Soc. Nephrol., December 1, 2007; 18(12): 3060 - 3066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Hampe, R. Nalini, M. R. Maldonado, T. R. Hall, G. Garza, D. Iyer, and A. Balasubramanyam Association of Amino-Terminal-Specific Antiglutamate Decarboxylase (GAD65) Autoantibodies with {beta}-Cell Functional Reserve and a Milder Clinical Phenotype in Patients with GAD65 Antibodies and Ketosis-Prone Diabetes Mellitus J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 462 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Kim, E. Y. Kim, J. Cerny, and K. D. Moudgil Antibody Responses to Mycobacterial and Self Heat Shock Protein 65 in Autoimmune Arthritis: Epitope Specificity and Implication in Pathogenesis J. Immunol., November 15, 2006; 177(10): 6634 - 6641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Raju, J. Foote, J. P. Banga, T. R. Hall, C. J. Padoa, M. C. Dalakas, E. Ortqvist, and C. S. Hampe Analysis of GAD65 Autoantibodies in Stiff-Person Syndrome Patients J. Immunol., December 1, 2005; 175(11): 7755 - 7762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. S. Wong, L. Wen, M. Tang, M. Ramanathan, I. Visintin, J. Daugherty, L. G. Hannum, C. A. Janeway Jr, and M. J. Shlomchik Investigation of the Role of B-Cells in Type 1 Diabetes in the NOD Mouse Diabetes, October 1, 2004; 53(10): 2581 - 2587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Guo, P. N. Pichurin, J. C. Morris, B. Rapoport, and S. M. McLachlan "Naked" Deoxyribonucleic Acid Vaccination Induces Recognition of Diverse Thyroid Peroxidase T Cell Epitopes Endocrinology, August 1, 2004; 145(8): 3671 - 3678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wulff, H.-G. Knaus, M. Pennington, and K. G. Chandy K+ Channel Expression during B Cell Differentiation: Implications for Immunomodulation and Autoimmunity J. Immunol., July 15, 2004; 173(2): 776 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Padoa, J. P. Banga, A.-M. Madec, M. Ziegler, M. Schlosser, E. Ortqvist, I. Kockum, J. Palmer, O. Rolandsson, K. A. Binder, et al. Recombinant Fabs of Human Monoclonal Antibodies Specific to the Middle Epitope of GAD65 Inhibit Type 1 Diabetes-Specific GAD65Abs Diabetes, November 1, 2003; 52(11): 2689 - 2695. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
