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

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 to 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 analysing 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.