cdr3

Evidence has shown that antibodies with unusually long CDR H3 regions may be a more effective defense against disease than typical antibodies. In cattle, 10% of antibodies have such ultralong CD3 H3 regions. Deep sequencing reveals a remarkable complexity of cysteines. Correspondingly, crystal structure reveals these CDR H3s form a very unusual architecture composed of a β strand “stalk” that supports a structurally diverse, disulfide-bonded “knob” domain, that can be elicited to recognize defined antigens. Through combinations of somatically generated disulfides, these ultralong CDR H3s can fold into a diversity of minidomains. These cow antibodies look interesting for their potential to zero on those targets that haven’t been successfully targeted by traditional antibodies, for example, the GPCRs, that have been intractable for antibody therapeutic development in the past. https://www.creative-biolabs.com/humanization-of-bovine-ultralong-cdr3-antibodies.html