Potential of endogenous peptides to induce immunological reactions as observed in type I diabetes, a study in mice

The initiation of the immunological processes leading to type I diabetes is still not understood. The potential of endogenous peptides to induce autoimmune reactions was investigated. Peptides generated in the beta-cell by proteolysis could bypass antigen processing by binding to MHC molecules. Selfreactive T and B lymphocytes could be activated by these MHC peptide complexes. The antibody production of peptide-induced B lymphocytes was investigated in mice. Insulin A chain, B chain, C-peptide or amylin were tested for potential induction of antibodies to antigens other than the immunizing peptide. Lymph node B lymphocytes were characterized with an avidin at solid phase ELISA-spot assay. In BALB/c mice insulin A chain induced more spots to B29biotin- and to B1biotinDOP insulin than to A chain itself (P < 0.01, each). Spots to insulin were not inhibited by insulin A chain. Spots to B1DOP insulin were not inhibited by A chain or insulin, excluding crossreaction. Inbred strains of mice with H-2d but not with H-2k or H-2b showed the effect. Application of A chain without adjuvant produced the effect. The antigens recognized by A chain-induced B lymphocytes had to be included in the natural IgM antibody repertoire of the spleen. The study supports the hypothesis that endogenous breakdown peptides can bypass antigen processing resulting in an autoreactive T-B cell interaction. A potential to induce type I diabetes could exist.