Antibody homotypic interactions are encoded by germline light chain complementarity determining region 2.

ABSTRACT: The utilization of avidity to drive and tune functional responses is fundamental to antibody biology and often underlies the mechanisms of action of monoclonal antibody drugs. There is increasing evidence that antibodies leverage homotypic interactions to enhance avidity, often through weak transient interfaces whereby self-association is coupled with target binding. Here, we comprehensively map the Fab–Fab interfaces of antibodies targeting DR5 and 4-1BB that utilize homotypic interaction to promote receptor activation and demonstrate that both antibodies have similar self-association determinants primarily encoded within a germline light chain complementarity determining region 2 (CDRL2). We further show that these determinants can be grafted onto antibodies of distinct target specificit

SUBMITTER: Leonard B 

PROVIDER: S-EPMC9191654 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature