Restricted blocking of cytotoxic T-cell function by anti-H-2K/D antibodies

Antibodies specific for H-2K and H-2D, the murine major histocompatibility complex (MHC)-encoded class I antigens, can block cytotoxic T (Tc)-cell function. Antibodies specific for the Tc cell and not the target cell have been used to map inhibition to the effector cell, suggesting a role for class I antigens in Tc-cell function. These antibody effects have been demonstrated for both alloreactive and MHC-restricted Tc cells, but inhibition has only been revealed by measuring cytotoxicity in a short-term assay. Using the neutral red assay for cytotoxicity, blocking effects evident after a 1.5-hr assay were lost by 2.5 hr. For some Tc-cell responses, only anti-H-2K antibodies have been found to be inhibitory, despite evidence of the expression of both H-2K and H-2D molecules on these cells. Some Tc-cell populations can be blocked by antibodies specific for both the H-2K and H-2D molecules. B10.A(4R) anti-Sendai Tc cells can be inhibited by anti-H-2Kk antibodies, but five different anti-H-2Db antibodies have been ineffective inhibitors. In contrast, B10.A(4R) anti-ectromelia Tc cells can be inhibited very effectively by each of these anti-H-2Db antibodies, as well as by anti-H-2Kk antibodies. Anti-H-2 antibodies also inhibit the function of cloned alloreactive Tc-cell lines such that the inhibitory capacity of antibodies specific for K versus D determinants appears to be consistent and specific for each Tc-cell line. A long-term Tc-cell clone, AR1, has been inhibited specifically by anti-H-2Kb and not anti-H-2Db antibodies, suggesting a clonally 'restricted' phenomenon.