Human and mouse monoclonal antibodies to blood group A substance, which are nearly identical immunochemically, use radically different primary sequences.
A human monoclonal antibody (HuA) specific for blood group A substance with two fucose groups was found to be immunochemically almost identical with that of a previously characterized mouse monoclonal anti-A, AC-1001. The VH and VL chain cDNAs of HuA were sequenced and compared with those of AC-1001. The human and mouse antibodies used VH and Vk genes that came from different families and shared minimal nucleotide and amino acid sequence identity. Thus, two antibodies from two different species can use evolutionarily unrelated sequences to bind the same carbohydrate epitope. The cloned HuA VH and VL genes were then transfected into a mouse myeloma cell line and re-expressed, together, and each separately with an irrelevant VH or VL. Only the original HuA VH and Vk had anti-A activity, demonstrating that both the heavy and light chains contributed to specificity.
Nickerson
K G
KG
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Tao
M H
MH
Chen
H T
HT
Larrick
J
J
Kabat
E A
EA
D000017:ABO Blood-Group System / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology; D000918:Antibody Specificity / Q000235:genetics*; D001483:Base Sequence; D002240:Carbohydrate Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D005643:Fucose / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000276:immunology; D011233:Precipitin Tests; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D009844:Oligosaccharides; D005643:Fucose