A Highly Conserved Interspecies VH in the Human Genome

Idiotype conservation between human and mouse antibodies has been observed in association with various infectious and autoimmune diseases. We have isolated a human anti-idiotypic antibody to a mouse monoclonal anti-IgE antibody (BSW17) suggesting a conserved interspecies idiotype associated with an anti-IgE response. To find the homologue of BSW17 in the human genome we applied the guided selection strategy. Combining VH of BSW17 with a human VL repertoire resulted in three light chains. The three VL chains were then combined with a human VH repertoire resulting in three clones specific for human IgE. Surprisingly, one clone, Hu41, had the same epitope specificity and functional in vitro activity as BSW17 and VH complementarity-determining regions identical with that of BSW17. Real-time PCR analysis confirmed the presence of the Hu41 VH sequence in the human genome. These data document the first example of the isolation of a human antibody where high sequence similarity to the original murine VH sequence is associated with common antigen and epitope specificity.