Immune response genes have a variable influence on the selection of antigenic foreign and self determinants of insulin.

Abstract

We studied the proliferative response of mouse T lymphocytes to determinants on ungulate insulins. The immunopotency of defined determinants on the molecule was found to be regulated by three factors: the immune response genes of the immunized mouse, the mode of presentation of insulin on cells or in adjuvant, and the intramolecular cooperativity between different determinants on the insulin molecule. Autosensitization against self determinants was observed under specific conditions. These findings emphasize the variable expression of immune response genes. Immune response (Ir) genes linked to the major histocompatibility complex (MHC) appear to restrict the response of T

Genetic control of autoimmune encephalomyelitis and recognition of the critical nonapeptide moiety of myelin basic protein in guinea pigs are exerted through interaction of lymphocytes and macrophages

“…We have found that (H-2k x H-2b)F1 hybrid mice primed in vivo by inoculation with bovine insulin in CFA will respond in vitro equally well to bovine insulin-pulsed M@ of either H-2b high-responder or H-2k low-responder strains of origin (manuscript in preparation). Furthermore, the Ir phenotype of the response to insulin in mice was found to be influenced by mode of immunization and intramolecular cooperation between antigenic determinants, as well as by MHC genes [17]. Similar findings of variable Ir phenotype have been reported for other antigens under control of MHC genes, such as lysozyme [26] or the synthetic peptide GAT [MI.…”

“…It has been observed that Ir phenotypes to insulin [17] or to a synthetic peptide antigen such as L-glutamic a~i d~~-~-a l a n i n e~~-~-t y r osine3'(GAT) [18] may be modified considerably by primary immunization with antigen-pulsed M a . Therefore, we investigated whether actual recognition and triggering of lymphocytes against the NP determinant could be achieved through primary immunization in vivo with antigen-pulsed M a .…”

“…Thus, Ir gene control of the response to the NP determinant of BP seems to differ from that seen in the responses to insulin [17] or to GAT in mice [MI.…”

Autoantibodies to Insulin Receptor Spontaneously Develop as Anti-Idiotypes in Mice Immunized with Insulin

“…Median test, P = .024. 19. Iguanas were sighted on their sleeping perches at night by means of a 200,000-candlepower hand-held light; they were observed from a boat passing along the lakeshore.…”

Peptide therapy for Type I diabetes: the immunological homunculus and the rationale for vaccination

“…Our pre-clinical studies of Type I diabetes actually began with an investigation of the effect of immune response genes on the T-cell response to the insulin molecule [22]. Ruth Maron and Dana Elias, who was doing her PhD thesis jointly with Yoram Shechter and myself at the time, showed that antibodies to the insulin receptor could arise spontaneously in the course of autoimmunization to insulin [23].…”