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PMID: 20139986 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Chromogranin A is an autoantigen in type 1 diabetes.

Nature immunology ·Vol. 11 ·No. 3 ·2010-03-00 ·Pages 225-31

Stadinski BD, Delong T, Reisdorph N, Reisdorph R, Powell RL, Armstrong M, Piganelli JD, Barbour G, Bradley B, Crawford F, Marrack P, Mahata SK, Kappler JW, Haskins K

Abstract

Autoreactive CD4(+) T cells are involved in the pathogenesis of many autoimmune diseases, but the antigens that stimulate their responses have been difficult to identify and in most cases are not well defined. In the nonobese diabetic (NOD) mouse model of type 1 diabetes, we have identified the peptide WE14 from chromogranin A (ChgA) as the antigen for highly diabetogenic CD4(+) T cell clones. Peptide truncation and extension analysis shows that WE14 bound to the NOD mouse major histocompatibility complex class II molecule I-A(g7) in an atypical manner, occupying only the carboxy-terminal half of the I-A(g7) peptide-binding groove. This finding extends the list of T cell antigens in type 1 diabetes and supports the idea that autoreactive T cells respond to unusually presented self peptides.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Animals Autoantigens/immunology Chromogranin A/immunology Diabetes Mellitus, Type 1/immunology Epitopes/immunology HLA-A Antigens Insulin-Secreting Cells/immunology Mass Spectrometry Mice Mice, Inbred NOD Mice, Knockout Molecular Sequence Data Peptide Fragments/immunology
Chemicals
Autoantigens Chromogranin A Epitopes HLA-A Antigens Peptide Fragments WE14 protein, mouse
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Stadinski Brian D
Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, Colorado, USA.
Delong Thomas
Reisdorph Nichole
Reisdorph Richard
Powell Roger L
Armstrong Michael
Piganelli Jon D
Barbour Gene
Bradley Brenda
Crawford Frances
Marrack Philippa
Mahata Sushil K
Kappler John W
Haskins Kathryn
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1844
Published
2010-03-00
Epub
2010-00-07
Pages
225-31
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3166626
Subset
IM
Grants
NCRR NIH HHS · S10RR023703 · United States
NIDDK NIH HHS · R01 DK050561-10 · United States
NIAID NIH HHS · 5 U19-AI050864 · United States
Howard Hughes Medical Institute · United States
NIAID NIH HHS · T32 AI007405 · United States
NIDDK NIH HHS · R01 DK50561 · United States
NIAID NIH HHS · R01 AI017134 · United States
NIDDK NIH HHS · R01 DK050561-09 · United States
NIAID NIH HHS · U19 AI050864 · United States
NIAID NIH HHS · R01 AI17134 · United States
NCRR NIH HHS · S10 RR023703 · United States
NIAID NIH HHS · T32 AI007405-10 · United States
NIAID NIH HHS · T32 AI007405-08 · United States
NIAID NIH HHS · R01 AI018785 · United States
NIDDK NIH HHS · P30 DK057516 · United States
NIAID NIH HHS · T32 AI007405-09 · United States
NIDDK NIH HHS · R01 DK050561 · United States
NIAID NIH HHS · R01 AI18785 · United States
NIDDK NIH HHS · R01 DK050561-11 · United States
NIAID NIH HHS · R01 AI018785-29 · United States
NIAID NIH HHS · P01 AI022295 · United States
External Links
PubMed source DOI: 10.1038/ni.1844 PMC Full Text View journal details
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