Islet cell antigens and autoantigen(s): Monoclonal antibodies and further characterization.

ABSTRACT

A novel series of murine monoclonal antibodies to islet cells (I-45, I-51, I-52 and I-39) have been generated using human insulinoma homogenate as the immunogen in order to characterize pathogenetically relevant islet cell autoantigen(s). Differentiation antigens recognized by these islet cell monoclonal antibodies displayed varied cytological distribution (pan-islet or peripheral mantle only). Monoclonal antibody I-45 reacted with all endocrine subsets of the pancreatic islet, similar to the reactivity of islet cell autoantibody positive sera from type I diabetes subjects. Preexposure to pH2 abolished the immunoreactivity of the autoantigen; I-45 antigen was also sensitive to low pH. Preexposure to 100° C for 1 h did not significantly alter the immunoreactivity of islet antigens recognized by ICAb positive patient sera and monoclonal antibody 1-39, thus demonstrating the extraordinary heat stability of the corresponding epitopes; those recognized by I-45 were less heat stable. Islet cells were found to share I-45 differentiation antigen(s)/epitope(s) with other neuroendocrine cells, viz. amerior pituitary, adrenal medulla and gut endocrine cells.