Monoclonal antiidiotypic antibodies neutralize cytotoxic effects of anti-alphaGal antibodies
Koren, E.; Milotic, F.; Neethling, F.A.; Koscec, M.; Fei, D.; Kobayashi, T.; Taniguchi, S.; Cooper, D.K.
Transplantation 62(6): 837-843
1996
ISSN/ISBN: 0041-1337 PMID: 8824486 Document Number: 459291
The aims of this study were to produce and characterize mouse monoclonal antiidiotypic antibodies (AIAs) that specifically bind human antipig (anti-alpha-Gal) 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-alpha-Gal 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 gt 48 hr. The cytotoxicity studies also indicated that there are at least two dominant idiotypes expressed in the human anti-alpha-Gal population. We conclude that AIAs against anti-alpha-Gal antibodies could be successfully used in (1) preoperative characterization of a recipient's anti-alpha-Gal profile, (2) prevention of hyperacute rejection of a pig organ, and (3) specific immunosuppression through elimination of anti-alpha-Gal-producing B lymphocytes.