Mechanism of MHC class II restriction in the interaction between specific suppressor and responder T cells in a proliferative response: Ia interaction with a putative anti-self receptor, expressed on pre-activated responder cells.

For the inhibition of T-lymphocyte proliferation in mixed lymphocyte culture (MLC) by in vivo alloantigen-induced specific T-suppressor cells (Ts), the Ts and responder cells must have major histocompatibility complex (MHC) class II identity, either in I-C or in I-A + I-E. In the case of I-C, the molecule is on the surface of the Ts and not on the surface of the stimulator or responder cells. This lack of I-C on the responder cells occurs even after pre-activation by antigen. I-J on the Ts is unimportant in the present system. By blocking the Ts surface molecules with antibody, it was shown that the two Ts genetic restrictions were due to distinct Ts subsets, bearing I-C in one case and I-A + I-E in the other. Pretreatment of the Ts with anti-I-C antibodies (without complement) did not prevent specific Ts binding to the alloantigen, as shown by absorption on monolayers. However, it blocked the ability of the Ts to cause suppression and this could be reversed by removal of the antibody with pronase. The responder population, when pre-activated, could be fractionated by absorbing on monolayers of syngeneic Ts. Under these conditions, the cells sensitive to suppression adhered to the monolayer, while the non-adherent cell could not be suppressed. It is proposed that a receptor, to an Ia molecule (I-C or I-A + I-E) of the Ts, appears on the surface of the pre-activated responder T cell and that this is required for the genetically restricted interaction between the responder cell and the Ts.