SUPERANTIGEN-DEPENDENT, CELL-MEDIATED CYTOTOXICITY INHIBITED BY MHC CLASS-I RECEPTORS ON T-LYMPHOCYTES

Bacterial superantigens bind with high affinity to major histocompatibility complex (MHC) class II antigens on antigen-presenting cells and with T cell antigen receptor (TCR) beta chains on T lymphocytes,which results in the T cell activation responsible for toxic shock syndrome and food poisoning, Many cytotoxic T lymphocyte (CTL) clones were shown to have receptors for human leukocyte antigen (HLA) class I molecules that inhibited superantigen-induced cytotoxicity against appropriate class I-bearing target cells. One type of inhibitory receptor, NKB1, was present on CD4(+) and CD8(+)TCR alpha beta(+) CTL clones and blocked the killing of staphylococcal enterotoxin B (SEB)-coated targets bearing certain polymorphic HLA-B molecules. Expression of HLA-A, -B, and -C molecules on the SEE-coated targets also protected against cytolysis mediated by many NKB1-negative T cell clones, suggesting the presence of additional inhibitory MHC class I receptors. These HLA class I receptors may limit tissue destruction and possibly autoimmunity caused by activated T lymphocytes.