Chromogranin A is an autoantigen in type 1 diabetes.
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.
Stadinski
Brian D
BD
Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, Colorado, USA.
Delong
Thomas
T
Reisdorph
Nichole
N
Reisdorph
Richard
R
Powell
Roger L
RL
Armstrong
Michael
M
Piganelli
Jon D
JD
Barbour
Gene
G
Bradley
Brenda
B
Crawford
Frances
F
Marrack
Philippa
P
Mahata
Sushil K
SK
Kappler
John W
JW
Haskins
Kathryn
K
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D053379:Chromogranin A / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D015234:HLA-A Antigens; D050417:Insulin-Secreting Cells / Q000276:immunology*; D013058:Mass Spectrometry; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*
D001324:Autoantigens; D053379:Chromogranin A; D000939:Epitopes; D015234:HLA-A Antigens; D010446:Peptide Fragments; C000604951:WE14 protein, mouse