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 …

MA Payton, CJ Hawkes… - The Journal of clinical …, 1995 - Am Soc Clin Investig
MA Payton, CJ Hawkes, MR Christie
The Journal of clinical investigation, 1995Am Soc Clin Investig
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 …
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.
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The Journal of Clinical Investigation