Modulation by antiidiotypic monoclonal antibodies of immune lysis mediated by anti-HLA monoclonal antibodies

The mAb R18-9 recognizes a cross-reacting idiotope outside the Ag-combining site of the syngeneic anti HLA-DQw3 mAb KS13, whereas the mAb R1-38, KO3-34, KO3-256, and KO3-335 recognize spatially close private idiotopes within the Ag-combining site of mAb KS13. All the analyzed Id require the association of the H and L chain of mAb KS13 for their expression. The mAb R1-38 and R18-9 were shown to markedly differ in their ability to modulate immune lysis of target cells mediated by mAb KS13. mAb R18-9 did not affect C-dependent lysis of cultured B lymphoid cells WALK mediated by mAb KS13, but enhanced cell-dependent mAb KS13-mediated lysis. mAb R1-38 inhibited both C and cell-dependent lysis mediated by mAb KS13. The effect was influenced by the incubation conditions. mAb R1-38 completely inhibited lysis when it was preincubated with mAb KS13 before being added to target cells, inhibited it partially when it was added simultaneously with mAb KS13 to target cells and did not affect it when added to target cells which had been preincubated with mAb KS13. Neither mAb R1-38 nor R18-9 in combination with mAb KS13 modulated T cell proliferation induced by allogeneic HLA mismatched lymphocytes. The system we have described may represent a useful in vitro model to investigate the mechanism(s) by which antiidiotypic antibodies may influence the outcome of organs transplanted in recipients with a history of humoral presensitization to donor's HLA Ag.