A comparison of human and macaque (Macaca mulatta) immunoglobulin germline V regions and its implications for antibody engineering

Abstract

Seventy-five V regions encoded by the sequenced genome of one Macaca mulatta specimen have been identified by homology and paired with similar human counterparts. When the human V region of each pair presented no allelic polymorphism, it was directly compared with its homolog. This was the case for 37 pairs and percents of identity ranged between 84-97%. When the human V region presented allelic polymorphism, this polymorphism was found to be significantly smaller (p < 0.0001, p < 0.0001, p = 0.03 for IGHV, IGLV, IGKV regions respectively), 4.2-fold on average, than the differences observed between human and macaque V regions. Similar results were obtained when analyzing framework regions (FRs) only. These results, in agreement with others, demonstrate the existence of differences between human and macaque V regions, confirm the need for the humanization of macaque V regions intended for therapeutic use and call into question the validity of patents relying on the " undistinguishable" character of human and macaque V regions or FRs. © 2010 Landes Bioscience.