Insulin-specific suppressor T cell factors.
Murine antibody responses to heterologous insulins are controlled by MHC-linked immune response genes. Although nonresponder mice fail to make antibody when injected with nonimmunogenic variants of insulin, we have recently shown that nonimmunogenic variants stimulate radioresistant, Lyt- 1+2- helper T cells that support secondary antibody responses. However, the helper activity can not be detected unless dominant, radiosensitive Lyt-1-2+, I-J+ suppressor T cells are removed. In this paper we report that extracts of primed Lyt-2+ suppressor T cells contain insulin-specific suppressor factors (TsF) that are capable of replacing the activity of suppressor T cells in vitro. The activity of these factors is restricted by MHC-linked genes that map to the I-J region, and immunoadsorption studies indicated that they bind antigen and bear I-J-encoded determinants. Insulin-specific TsF consists of at least two chains, one-bearing I-J and the other the antigen-binding site. Furthermore, mixing of isolated chains from different strains of mice indicates that the antigenic specificity is determined by the antigen-binding chain and the MHC restriction by the H-2 haplotype of the source of the non-antigen-binding, I-J+ chain. Moreover, mixtures containing antigen-binding chain from allogeneic cell donors and I-J+ chain from responder cell donors have activity in cultures containing responder lymphocytes. This suggests that preferential activation of suppressor T cells, rather than differential sensitivity to suppression, results in the nonresponder phenotype to insulin.
P E
PE
Jensen
J A
JA
Kapp
D000818:Animals; D002236:Carbohydrate Conformation; D002457:Cell Extracts / Q000032:analysis; D000939:Epitopes / Q000032:analysis*; D006183:H-2 Antigens / Q000235:genetics; D006649:Histocompatibility Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II; D007163:Immunosorbent Techniques; D007328:Insulin / Q000276:immunology* / Q000378:metabolism; D061389:Insulin, Regular, Pork; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013491:Suppressor Factors, Immunologic / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
D002457:Cell Extracts; D000939:Epitopes; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C043911:I-J-antigen; D007328:Insulin; D061389:Insulin, Regular, Pork; D013491:Suppressor Factors, Immunologic; C000006:insulin, neutral