Activation of antigen-specific suppressor T lymphocytes in man involves dual recognition of self class I MHC molecules and Leu-4/T3-associated structures on the surface of inducer T lymphocytes.
We showed previously that fresh Leu-2+ T cells respond to autologous antigen-primed Leu-3+ T cells by proliferation and differentiation into suppressor T cells (Ts) that specifically inhibit the response of fresh Leu-3+ cells to the original priming antigen. This study was undertaken to characterize the role of various cell surface molecules expressed by antigen-primed Leu-3+ cells in their activation of Leu-2+ Ts cells. Alloactivated Leu-3+ blasts were treated in the absence of complement with a variety of monoclonal antibodies recognizing distinct antigens on human lymphoid cells, and then were examined for their functional effects on fresh autologous T cells. Prior treatment of Leu-3+ blasts with anti-Leu-4 or anti-HLA-A,B,C framework antibodies, but not with anti-Leu-1, anti-Leu-3, anti-Leu-5, or anti-HLA-DR framework-specific antibodies, not only blocked proliferation of fresh Leu-2+ cells, it also prevented their differentiation into Ts cells. Furthermore, after their activation by Leu-3+ blasts, Leu-2+ Ts cells inhibited the response of fresh Leu-3+ cells from only those individuals who shared HLA-A,B phenotypes with suppressor-effector cells. These results suggest that both the inductive and effector phases of suppression involve dual recognition of autologous class I MHC molecules and structures associated with the Leu-4 (T3) molecule on the surface of antigen-reactive Leu-3+ cells.
D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology*; D001667:Binding, Competitive; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D006680:HLA Antigens