Genetics of insulin-specific helper and suppressor T cells in nonresponder mice.
The role of insulin-specific helper and suppressor T cells in the H-2-linked genetic control of antibody responses to heterologous insulins was examined in vitro. These data demonstrate that pork insulin stimulates both primed helper T cells and dominant suppressor T cells in all nonresponder strains tested. Thus, the nonresponder phenotype is attributed to the activation of specific suppressor T cells rather than to an absence of helper T cell activity. Examination of the antigenic cross-reactivity patterns of pork insulin-primed helper and suppressor T cells in various strains demonstrates that fine specificity of the helper T cells differs from that of the suppressor T cells and that the patterns of antigenic cross-reactivity of these subpopulations are controlled by the H-2 gene complex. Furthermore, in a given strain of mice variants of insulin that stimulate helper T cells that cross-react with mouse insulin also stimulate dominant suppressor T cells that cross-react with mouse insulin. Such variants of insulin are perceived as nonimmunogenic. These observations raise the possibility that nonresponsiveness that is controlled by H-2 linked genes results from the activation of regulatory mechanisms involved in maintaining self-tolerance.
P E
PE
Jensen
J A
JA
Kapp
D000818:Animals; D003429:Cross Reactions; D000939:Epitopes / Q000235:genetics*; D006183:H-2 Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D007114:Immunization; D007328:Insulin / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013045:Species Specificity; D013552:Swine; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D000949:Histocompatibility Antigens Class II; D007328:Insulin