Circulating Preproinsulin Signal Peptide-Specific CD8 T Cells Restricted by the Susceptibility Molecule HLA-A24 Are Expanded at Onset of Type 1 Diabetes and Kill -Cells
نویسندگان
چکیده
منابع مشابه
Circulating Preproinsulin Signal Peptide–Specific CD8 T Cells Restricted by the Susceptibility Molecule HLA-A24 Are Expanded at Onset of Type 1 Diabetes and Kill β-Cells
Type 1 diabetes results from T cell-mediated β-cell destruction. The HLA-A*24 class I gene confers significant risk of disease and early onset. We tested the hypothesis that HLA-A24 molecules on islet cells present preproinsulin (PPI) peptide epitopes to CD8 cytotoxic T cells (CTLs). Surrogate β-cell lines secreting proinsulin and expressing HLA-A24 were generated and their peptide ligandome ex...
متن کاملRecognition of Human Proinsulin Leader Sequence by Class I–Restricted T-Cells in HLA-A*0201 Transgenic Mice and in Human Type 1 Diabetes
OBJECTIVE A restricted region of proinsulin located in the B chain and adjacent region of C-peptide has been shown to contain numerous candidate epitopes recognized by CD8(+) T-cells. Our objective is to characterize HLA class I-restricted epitopes located within the preproinsulin leader sequence. RESEARCH DESIGN AND METHODS Seven 8- to 11-mer preproinsulin peptides carrying anchoring residue...
متن کاملHLA-restricted and Antigen-specific CD8+ T Cell Responses by K562 Cells Expressing HLA-A*0201
Background: Identification of antigen-specific T cells has yielded valuable information on pathologic process and the disease state. Assays for quantification of inflammatory cytokines or lytic-granule molecules have been generally used to evaluate antigen specific T cell response, however their applicability have been hampered due to the limited source of autologous antigen-presenting target c...
متن کاملCTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope.
The final pathway of beta cell destruction leading to insulin deficiency, hyperglycemia, and clinical type 1 diabetes is unknown. Here we show that circulating CTLs can kill beta cells via recognition of a glucose-regulated epitope. First, we identified 2 naturally processed epitopes from the human preproinsulin signal peptide by elution from HLA-A2 (specifically, the protein encoded by the A*0...
متن کاملCytotoxic T cell induction against human malignant melanoma cells using HLA-A24-restricted melanoma peptide cocktail.
Many human leukocyte antigen (HLA)-class I (mainly A*0201)-restricted peptide-specific cytotoxic T cells (CTLs) have been derived from peripheral blood lymphocytes (PBLs) of melanoma patients. However, few studies regarding HLA-A*2402-restricted melanoma-associated peptides have been performed, because HLA-A24 is not a common allele in Caucasians. In this study, we investigated the specific CTL...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Diabetes
سال: 2012
ISSN: 0012-1797,1939-327X
DOI: 10.2337/db11-1520