Monoclonal antiidiotypic antibodies neutralize cytotoxic effects of anti-alphaGal antibodies.
The aims of this study were to produce and characterize mouse monoclonal antiidiotypic antibodies (AIAs) that specifically bind human antipig (anti-alphaGal) antibodies and to select those AIAs that neutralize the cytotoxicity of human or baboon serum to pig (PK15) cells. Mice were immunized with human anti-pig 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 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-alphaGal population. We conclude that AIAs against anti-alphaGal antibodies could be successfully used in 1) preoperative characterization of a recipient's anti-alphaGal profile, (2) prevention of hyperacute rejection of a pig organ, and (3) specific immunosuppression through elimination of anti-alphaGal-producing B lymphocytes.
Koren
E
E
Oklahoma Medical Research Foundation, Oklahoma City, USA.
Milotic
F
F
Neethling
F A
FA
Koscec
M
M
Fei
D
D
Kobayashi
T
T
Taniguchi
S
S
Cooper
D K
DK
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000910:Antibodies, Heterophile / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D003429:Cross Reactions; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010215:Papio / Q000097:blood / Q000276:immunology; D013045:Species Specificity; D013552:Swine / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology; D014312:Trisaccharides / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D014312:Trisaccharides; C076569:alpha-galactosyl epitope