Long CDR3s. The complementarity determining regions (CDRs) of antibodies mediate binding to the target antigen. The CDR3 of the heavy chain often confers the most binding surface. Species like mice and humans have relatively short CDR3s, whereas cows have the longest CDR3s known, and can range up to 70 amino acids in length.
Unique structural diversity. The long CDR3s form unique domains that protrude from the antibody surface, enabling binding to challenging recessed epitopes. The ultralong CDR3 subset has disulfide bonded mini-domains that resemble venomous peptides which potently bind ion channels and GPCRs. These unique properties could make cow antibodies an enabling scaffold for targeting these difficult antigens.