ArticleDiabetes2009
Recognition of human proinsulin leader sequence by class I-restricted T-cells in HLA-A*0201 transgenic mice and in human type 1 diabetes.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Pivotal epitopes for islet antigen-specific CD8Immunologic research · 2025Article
- The many faces of islet antigen-specific CD8 T cells: clues to clinical outcome in type 1 diabetes.Immunology and cell biology · 2021Review
- A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes.Frontiers in immunology · 2021Article
- Combinatorial detection of autoreactive CD8Diabetologia · 2018Article
- Increase in Pancreatic Proinsulin and Preservation of β-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset.Diabetes · 2017Article
- Narrowing in on the anti-β cell-specific T cells: looking 'where the action is'.Current opinion in endocrinology, diabetes, and obesity · 2017Review
- Characterization of the autoimmune response against the nerve tissue S100β in patients with type 1 diabetes.Clinical and experimental immunology · 2015Article
- HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 monochain transgenic/H-2 class I null mice: novel versatile preclinical models of human T cell responses.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Cell-based interventions to halt autoimmunity in type 1 diabetes mellitus.Clinical and experimental immunology · 2013Review
- Identification of conserved and HLA promiscuous DENV3 T-cell epitopes.PLoS neglected tropical diseases · 2013Article
- Islet autoantigens: structure, function, localization, and regulation.Cold Spring Harbor perspectives in medicine · 2012Review
- Article
- Antigen targets of type 1 diabetes autoimmunity.Cold Spring Harbor perspectives in medicine · 2012Review
- Single insulin-specific CD8+ T cells show characteristic gene expression profiles in human type 1 diabetes.Diabetes · 2011Article
- Viruses and cytotoxic T lymphocytes in type 1 diabetes.Clinical reviews in allergy & immunology · 2011Review
- Pathogenic and regulatory T cells in type 1 diabetes: losing self-control, restoring it, and how to take the temperature.Current diabetes reports · 2011Review
- Antigen-based immune therapeutics for type 1 diabetes: magic bullets or ordinary blanks?Clinical & developmental immunology · 2011Article
- T cell recognition of autoantigens in human type 1 diabetes: clinical perspectives.Clinical & developmental immunology · 2011Review
- Beta cell antigens in type 1 diabetes: triggers in pathogenesis and therapeutic targets.F1000 biology reports · 2010Article
- Ins2 deficiency augments spontaneous HLA-A*0201-restricted T cell responses to insulin.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveA 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
methodsSeven 8- to 11-mer preproinsulin peptides carrying anchoring residues for HLA-A1, -A2, -A24, and -B8 were selected from databases. HLA-A2-restricted peptides were tested for immunogenicity in transgenic mice expressing a chimeric HLA-A*0201/beta2-microglobulin molecule. The peptides were studied for binding to purified HLA class I molecules, selected for carrying COOH-terminal residues generated by proteasome digestion in vitro and tested for recognition by human lymphocytes using an ex vivo interferon-gamma (IFN-gamma) ELISpot assay.
resultsFive HLA-A2-restricted peptides were immunogenic in transgenic mice. Murine T-cell clones specific for these peptides were cytotoxic against cells transfected with the preproinsulin gene. They were recognized by peripheral blood mononuclear cells (PBMCs) from 17 of 21 HLA-A2 type 1 diabetic patients. PBMCs from 25 of 38 HLA-A1, -A2, -A24, or -B8 patients produced IFN-gamma in response to six preproinsulin peptides covering residues 2-25 within the preproinsulin region. In most patients, the response was against several class I-restricted peptides. T-cells recognizing preproinsulin peptide were characterized as CD8(+) T-cells by staining with peptide/HLA-A2 tetramers.
conclusionsWe defined class I-restricted epitopes located within the leader sequence of human preproinsulin through in vivo (transgenic mice) and ex vivo (diabetic patients) assays, illustrating the possible role of preproinsulin-specific CD8(+) T-cells in human type 1 diabetes.
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