Human and Mouse Monoclonal Antibodies to Blood Group A Substance, Which Are Nearly Identical Immunochemically, Use Radically Different Primary Sequences

Abstract

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.