Inhibition by sera and soluble antigens of T-cell-mediated cytotoxicity against leukaemia-associated antigens

Abstract

INTEREST in the regulation of T-cell-mediated cytotoxicity by the major histocompatibility complex (MHC) genes stems from the discovery of (1) an H–2 restriction of T-cell-mediated cytotoxicity, that is sensitising cells, effector cells and target cells need to be syngeneic at the H–2 locus, especially at the D and or K regions of the MHC^1–5 for effective killing and (2) inhibition of T-cell-mediated cytotoxic reactions against syngeneic tumours with alloantibodies to H–2 antigens specific for the tumour cells^6,7. Different origins have been proposed for the tumour-associated antigens (TAA), and the most favourable model is a modified H–2 antigen or an adaptor–antigen complex^4–7. This issue has important implications for tumour immunology, and so we have evaluated the validity of the inhibition of cytotoxicity by serum at the effector phase level; investigated afferent interference by serum of the cell-mediated cytotoxic response, and studied the inhibition of cell-mediated cytotoxic reactions with soluble antigens. We report here that there is a lack of H–2 restriction of T-cell-mediated cytotoxicity to TAA, and that TAA seems to differ from H–2 antigens. This implies that T-cell recognition is not entirely regulated by the MHC genes.