Format

Send to

Choose Destination
See comment in PubMed Commons below
Diabetes. 2011 Sep;60(9):2325-30. doi: 10.2337/db11-0288. Epub 2011 Jul 6.

Islet amyloid polypeptide is a target antigen for diabetogenic CD4+ T cells.

Author information

1
Integrated Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, Colorado, USA.

Abstract

OBJECTIVE:

To investigate autoantigens in β-cells, we have used a panel of pathogenic T-cell clones that were derived from the NOD mouse. Our particular focus in this study was on the identification of the target antigen for the highly diabetogenic T-cell clone BDC-5.2.9.

RESEARCH DESIGN AND METHODS:

To purify β-cell antigens, we applied sequential size exclusion chromatography and reverse-phase high-performance liquid chromatography to membrane preparations of β-cell tumors. The presence of antigen was monitored by measuring the interferon-γ production of BDC-5.2.9 in response to chromatographic fractions in the presence of NOD antigen-presenting cells. Peak antigenic fractions were analyzed by ion-trap mass spectrometry, and candidate proteins were further investigated through peptide analysis and, where possible, testing of islet tissue from gene knockout mice.

RESULTS:

Mass-spectrometric analysis revealed the presence of islet amyloid polypeptide (IAPP) in antigen-containing fractions. Confirmation of IAPP as the antigen target was demonstrated by the inability of islets from IAPP-deficient mice to stimulate BDC-5.2.9 in vitro and in vivo and by the existence of an IAPP-derived peptide that strongly stimulates BCD-5.2.9.

CONCLUSIONS:

IAPP is the target antigen for the diabetogenic CD4 T-cell clone BDC-5.2.9.

PMID:
21734016
PMCID:
PMC3161333
DOI:
10.2337/db11-0288
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center