Relationship of the 37,000- and 40,000-M(r) tryptic fragments of islet antigens in insulin-dependent diabetes to the protein tyrosine phosphatase-like molecule IA-2 (ICA512).
Sera from patients with insulin-dependent diabetes immunoprecipitate 64,000-M(r) proteins, distinct from glutamate decarboxylase, that are cleaved to 37,000- and 40,000-M(r) fragments by trypsin. We investigated possible relationships between 37,000- or 40,000-M(r) fragments of antigen and the tyrosine phosphatase-like protein, IA-2 (ICA512). Antibodies from nondiabetic relatives bound differentially to 37,000- and 40,000-M(r) fragments indicating presence of distinct epitopes. Precursors of these fragments could be separated on immobilized lectins, suggesting different carbohydrate content. Levels of antibodies to 40,000-M(r) fragments were strongly associated with those to the intracellular domain of IA-2. Recombinant intracellular domain of IA-2 blocked binding of antibodies to 40,000-M(r) fragments expressed by insulinoma cells and partially blocked binding to 37,000-M(r) fragments. Furthermore, trypsinization of recombinant intracellular domain of IA-2 generated proteolytic fragments of identical M(r) to the 40,000-M(r) fragments of insulinoma antigen; 37,000-M(r) fragments were not generated. Thus, 40,000-M(r) fragments of islet autoantigen are derived from a protein similar or identical to the tyrosine phosphatase-like molecule, IA-2. The 37,000-M(r) fragments are derived from a different, although related, protein.
Payton
M A
MA
Department of Medicine, King's College School of Medicine and Dentistry, London, United Kingdom.
Hawkes
C J
CJ
Christie
M R
MR
D000818:Animals; D000937:Antigen-Antibody Reactions; D000941:Antigens / Q000737:chemistry* / Q000276:immunology; D001324:Autoantigens; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002241:Carbohydrates / Q000032:analysis; D003001:Cloning, Molecular; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005190:Family; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D037102:Lectins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology; D016133:Polymerase Chain Reaction; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D051381:Rats; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D012016:Reference Values; D014357:Trypsin
D000941:Antigens; D001324:Autoantigens; D002241:Carbohydrates; D017931:DNA Primers; D037102:Lectins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516864:Ptprn protein, rat; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D014357:Trypsin; D005968:Glutamate Decarboxylase