Monoclonal antiidiotypic antibodies neutralize cytotoxic effects of anti-αGal antibodies

The aims of this study were to produce and characterize mouse monoclonal antiidiotypic antibodies (AIAs) that specifically bind human antipig (anti-aGal) antibodies and to select those AIAs that neutralize the cytotoxicity of human or baboon serum to pig (PK15) cells. Mice were immunized with human antipig antibodies, and hybridomas were produced using conventional techniques. From a total of 480 clones, 11 produced AIAs that bound with high affinity to human anti-αGa1 IgG and F(ab') 2 fragments, and individually reduced serum cytotoxicity to pig cells by 40 - 90%. Seven of the AIAs also bound to human peripheral B lymphocytes (that express the same idiotypes as the antibodies they produce). Several combinations of two or three AIAs provided 100% protection of PK15 cells. Selected AIAs injected intravenously into baboons reduced the cytotoxicity of subsequently drawn sera by 50-80% for >48 hr. The cytotoxicity studies also indicated that there are at least two dominant idiotypes expressed in the human anti-αGal population. We conclude that AIAs against anti-αGal antibodies could be successfully used in (1) preoperative characterization of a recipient's anti-αGal profile, (2) prevention of hyperacute rejection of a pig organ, and (3) specific immunosuppression through elimination of anti-αGal-producing B lymphocytes.