Expression of major histocompatibility antigens on pancreatic islet cells.

Abstract

Insulin-dependent diabetes mellitus is often accompanied by manifestations of autoimmunity and is frequently associated with certain HLA haplotypes, predominantly DR3 and DR4. Because the major histocompatibility antigens are important determinants of the immune response in various tissues, we have investigated their expression on the pancreatic islet cells. Human, mouse, or rat islets ofLangerhans, as well as lymphocytes or other differentiated cells, were biosynthetically labeled with radioactive amino acids, lysed in detergent, and immunoprecipitated with several antisera specific for major histocompatibility antigenic groups. The immunoprecipitates were analyzed by NaDodSo4/ polyacrylamide gel electrophoresis under reducing conditions followed by autoradiography. The major histocompatibility antigens corresponding to the H-2 K,D molecules in mice, the Hi-A in rats, and the HLA-A, -B, and -C in humans were precipitated from both islet and lymphocyte lysates and were accompanied by fi2-microglobulin. Binding of H-2 antibodies to islet cells was also confirmed by a radioligand assay using l'I-labeled protein A and by indirect immunofluorescence. Analyses in the fluorescence-activated cell sorter revealed that >95% of the cells in the beta-cellrich fraction were fluorescent, providing further evidence that the pancreatic beta cells express the major histocompatibility antigens. Monoclonal antibodies or mouse alloantisera against HLA-DR or Ia antigens did not react with labeled pancreatic islet cell proteins.

Immunological perspective of self versus tumor antigens: insights from the RIP‐gp model

“…The above work suggests that, while pancreatic islets constitutively express low levels of MHC class I (87, 88), the extent of this expression is insufficient for infiltration by CD8+ T cells. Similarly, using a NOD mouse that transgenically expresses the adenovirus E19 protein to inhibit surface MHC class I expression in the β cells, Yamanouchi et al .…”

Islet cell antibodies ? Theoretical and practical implications

“…The possible presence of B cell specific antigens which may be recognized in autoimmune diabetes is currently being studied with xenogenic [12] as well as monoclonal [25] antibodies. Such antibodies have proved useful in the biochemical analysis of transplantation antigens expressed on the B cells [26].…”

IFNγ/TNFα synergism in MHC class II induction: effect of nicotinamide on MHC class II expression but not on islet-cell apoptosis

“…Although most cells express MHC class I molecules, the expression of class II molecules is restricted to specialized antigen-presenting cells (APC). It has been suggested that the induction of MHC class II on nonlymphoid cells, such as pancreatic beta cells which do not normally express MHC class II molecules [6], could result in the initiation of autoimmunity [7]. Although controversies exist [8±10], it has been reported that islet beta cells from the patients with Type I diabetes mellitus or animals with autoimmune diabetes mellitus express MHC class II antigens [11±13].…”