Conserved epitopes in the protein tyrosine phosphatase family of diabetes autoantigens.
IA2 and phogrin are important targets of humoral and cell-mediated autoimmunity in type 1 diabetes in man. They belong to a conserved subfamily of transmembrane protein tyrosine phosphatases (PTPs) associated with the regulatory pathway of secretion. To examine potential cross-reactivity between PTP family members we tested sera from T1D patients for reactivity to IA2, and the Drosophila (FLYDA) and C. elegans (IDA) orthologs using radioimmunoprecipitation assays of (35)S Met-labeled in vitro translated products of the cytosolic domains of these proteins. Approximately 80% of sera reacted with at least one probe. Of these, 82.5% showed reactivity to human IA2, 74.1% to FLYDA, and 33.7% to IDA. The majority of sera that bound FLYDA and/or IDA also recognized IA2. This raises the possibility that in some cases reactivity to IA2 may have arisen by molecular mimicry.
Liu
Y
Y
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA.
Wenzlau
J M
JM
Yu
L
L
Patel
C
C
Eisenbarth
G S
GS
Hutton
J C
JC
Davidson
H W
HW
D000818:Animals; D000918:Antibody Specificity; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D016022:Case-Control Studies; D017124:Conserved Sequence / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004330:Drosophila / Q000201:enzymology / Q000235:genetics; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D005810:Multigene Family / Q000276:immunology / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017385:Sequence Homology
D001324:Autoantigens; D000939:Epitopes; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8