In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 16 ( 1999-08-03), p. 9311-9316
Abstract:
Spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice is the result of a CD4 + and CD8 + T cell-dependent autoimmune process directed against the pancreatic beta cells. CD8 + T cells play a critical role in the initiation and progression of diabetes, but the specificity and diversity of their antigenic repertoire remain unknown. Here, we define the structure of a peptide mimotope that elicits the proliferation, cytokine secretion, differentiation, and cytotoxicity of a diabetogenic H-2K d -restricted CD8 + T cell specificity (NY8.3) that uses a T cell receptor α (TCRα) rearrangement frequently expressed by CD8 + T cells propagated from the earliest insulitic lesions of NOD mice (Vα17-Jα42 elements, often joined by the N-region sequence M-R-D/E). Stimulation of splenic CD8 + T cells from single-chain 8.3-TCRβ-transgenic NOD mice with this mimotope leads to preferential expansion of T cells bearing an endogenously derived TCRα chain identical to the one used by their islet-associated CD8 + T cells, which is also identical to the 8.3-TCRα sequence. Cytotoxicity assays using islet-derived CD8 + T cell clones from nontransgenic NOD mice as effectors and peptide-pulsed H-2K d -transfected RMA-S cells as targets indicate that nearly half of the CD8 + T cells recruited to islets in NOD mice specifically recognize the same peptide/H-2K d complex. This work demonstrates that beta cell-reactive CD8 + T cells mount a prevalent response against a single peptide/MHC complex and provides one peptide ligand for CD8 + T cells in autoimmune diabetes.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.96.16.9311
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1999
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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