| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Microbiology and Immunology, and
Medicine (Division of Endocrinology), Albert Einstein College of Medicine, Bronx, NY 10461;
The Jackson Laboratory, Bar Harbor, ME 04609; and
Department of Microbiology and Infectious Diseases, and Julia McFarlane Diabetes Research Centre, Faculty of Medicine, Health Sciences Centre, University of Calgary, Calgary, Alberta, Canada
The NOD mouse is a model for autoimmune type 1 diabetes in humans. CD8+ T cells are essential for the destruction of the insulin-producing pancreatic 
cells characterizing this disease. AI4 is a pathogenic CD8+ T cell clone, isolated from the islets of a 5-wk-old female NOD mouse, which is capable of mediating overt diabetes in the absence of CD4+ T cell help. Recent studies using MHC-congenic NOD mice revealed marked promiscuity of the AI4 TCR, as the selection of this clonotype can be influenced by multiple MHC molecules, including some class II variants. The present work was designed, in part, to determine whether similar promiscuity also characterizes the effector function of mature AI4 CTL. Using splenocyte and bone marrow disease transfer models and in vitro islet-killing assays, we report that efficient recognition and destruction of cells by AI4 requires the cells to simultaneously express both H-2Db and H-2Kd class I MHC molecules. The ability of the AI4 TCR to interact with both H-2Db and H-2Kd was confirmed using recombinant peptide libraries. This approach also allowed us to define a mimotope peptide recognized by AI4 in an H-2Db-restricted manner. Using ELISPOT and mimotope/H-2Db tetramer analyses, we demonstrate for the first time that AI4 represents a readily detectable T cell population in the islet infiltrates of prediabetic NOD mice. Our identification of a ligand for AI4-like T cells will facilitate further characterization and manipulation of this pathogenic and promiscuous T cell population.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  Y.-G. Chen, F. Scheuplein, M. A. Osborne, S.-W. Tsaih, H. D. Chapman, and D. V. Serreze Idd9/11 Genetic Locus Regulates Diabetogenic Activity of CD4 T-Cells in Nonobese Diabetic (NOD) Mice Diabetes, December 1, 2008; 57(12): 3273 - 3280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mukhopadhaya, T. Hanafusa, I. Jarchum, Y.-G. Chen, Y. Iwai, D. V. Serreze, R. M. Steinman, K. V. Tarbell, and T. P. DiLorenzo Selective delivery of {beta} cell antigen to dendritic cells in vivo leads to deletion and tolerance of autoreactive CD8+ T cells in NOD mice PNAS, April 29, 2008; 105(17): 6374 - 6379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Takaki, M. P. Marron, C. E. Mathews, S. T. Guttmann, R. Bottino, M. Trucco, T. P. DiLorenzo, and D. V. Serreze HLA-A*0201-Restricted T Cells from Humanized NOD Mice Recognize Autoantigens of Potential Clinical Relevance to Type 1 Diabetes. J. Immunol., March 1, 2006; 176(5): 3257 - 3265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ueno, S. Cho, L. Cheng, Z. Wang, B. Wang, and Y. Yang Diabetes Resistance/Susceptibility in T Cells of Nonobese Diabetic Mice Conferred by MHC and MHC-Linked Genes J. Immunol., October 15, 2005; 175(8): 5240 - 5247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Lieberman, T. Takaki, B. Han, P. Santamaria, D. V. Serreze, and T. P. DiLorenzo Individual Nonobese Diabetic Mice Exhibit Unique Patterns of CD8+ T Cell Reactivity to Three Islet Antigens, Including the Newly Identified Widely Expressed Dystrophia Myotonica Kinase J. Immunol., December 1, 2004; 173(11): 6727 - 6734. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
