Identification of relevant peptides involved in the initiation and progression of autoimmune diabetes

鉴定参与自身免疫性糖尿病发生和进展的相关肽

基本信息

  • 批准号:
    9689765
  • 负责人:
  • 金额:
    $ 40.47万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-20 至 2022-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary We propose a collaborative project involving immunologists experienced in autoimmune diabetes, mass-spectrometrists, and endocrinologists-diabetologists. Our combined efforts are to specifically identify relevant peptides from beta cell proteins involved in the immunopathogenesis of type 1 diabetes. The project combines experimental studies in diabetes-prone mice that should lead to targeted evaluation of human samples. The ultimate goal is to identify peptides that form the substrate for the autoreactive MHC-II response that initiates and perpetuates the process. Important is to identify relevant diabetogenic antigens at different stages of the autoimmune reaction from pre-diabetes to the initial progression: it will include their characterization, source in beta cells, involvement in the disease process, and sites of presentation. Aim 1 consists of an identification of novel peptides derived from beta cell granules of both mice and humans. We examine vesicles isolated from beta cells with a major focus on crinosomes. Crinosomes and insulin dense core granules will be isolated during different stages of diabetes development, their peptides will be isolated and examined by sophisticated mass spectrometry with state of the art instrumentation and technology. We will place emphasis in unique structural or post translational changes in peptides and whether the panoply of them changes as the beta cell progresses into active diabetes. We also will examine vesicles and exocytosed products from human islets from recently diseased individuals. Aim 2 will be an immunological validation of novel peptides identified by mass spectrometry. Immunological and biochemical assays will be used to validate the ability of beta cell derived peptides to bind to I-Ag7 and activate T cells in vitro and in vivo. Aim 3 will be the Identification and validation of the MHC-II-bound peptidome in islets and secondary lymphoid organs. We plan to examine the peptidome eluted from MHC-II molecules expressed by phagocytes obtained from islets, peripheral lymph nodes, and spleens of the NOD mouse and to characterize/validate them as in Aims 1/2. This is the seminal test to prove an immunogenic peptide, that is, it's a positive identification bound in vivo to MHC-II alleles.
项目总结

项目成果

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EMIL Raphael UNANUE其他文献

EMIL Raphael UNANUE的其他文献

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{{ truncateString('EMIL Raphael UNANUE', 18)}}的其他基金

Identification of relevant peptides involved in the initiation and progression of autoimmune diabetes
鉴定参与自身免疫性糖尿病发生和进展的相关肽
  • 批准号:
    10246429
  • 财政年份:
    2018
  • 资助金额:
    $ 40.47万
  • 项目类别:
AUTOIMMUNE DIABETES: EARLY EVENTS IN ISLETS OF LANGERHANS
自身免疫性糖尿病:朗格汉斯岛的早期事件
  • 批准号:
    9197630
  • 财政年份:
    2015
  • 资助金额:
    $ 40.47万
  • 项目类别:
CHARACTERIZATION OF ANTIGENIC PEPTIDES PRESENTED BY I-AG7
I-AG7 呈现的​​抗原肽的表征
  • 批准号:
    8361393
  • 财政年份:
    2011
  • 资助金额:
    $ 40.47万
  • 项目类别:
IDENTIFICATION OF MODIFIED AND NATURAL HEL PEPTIDE FRAGMENTS PRESENTED BY MHC
MHC 呈现的修饰和天然 HEL 肽片段的鉴定
  • 批准号:
    8361330
  • 财政年份:
    2011
  • 资助金额:
    $ 40.47万
  • 项目类别:
ANTIGEN PROCESSING IN NITCIITA
NITCIITA 中的抗原处理
  • 批准号:
    8361361
  • 财政年份:
    2011
  • 资助金额:
    $ 40.47万
  • 项目类别:
IDENTIFICATION OF MODIFIED AND NATURAL HEL PEPTIDE FRAGMENTS PRESENTED BY MHC
MHC 呈现的修饰和天然 HEL 肽片段的鉴定
  • 批准号:
    8168678
  • 财政年份:
    2010
  • 资助金额:
    $ 40.47万
  • 项目类别:
PEPTIDES IDENTIFIED FROM THE TYPE I DIABETES ASSOCIATED MHC CLASS I-H2-KD
从 I 型糖尿病相关 MHC I-H2-KD 类中鉴定出的肽
  • 批准号:
    8168690
  • 财政年份:
    2010
  • 资助金额:
    $ 40.47万
  • 项目类别:
ANTIGEN PROCESSING IN NITCIITA
NITCIITA 中的抗原处理
  • 批准号:
    8168713
  • 财政年份:
    2010
  • 资助金额:
    $ 40.47万
  • 项目类别:
CHARACTERIZATION OF ANTIGENIC PEPTIDES PRESENTED BY I-AG7
I-AG7 呈现的​​抗原肽的表征
  • 批准号:
    8168793
  • 财政年份:
    2010
  • 资助金额:
    $ 40.47万
  • 项目类别:
Studies of Antigen Stimulation
抗原刺激的研究
  • 批准号:
    7846477
  • 财政年份:
    2009
  • 资助金额:
    $ 40.47万
  • 项目类别:

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