Antigen exposure leads to rigidification of germline antibody combining site.

Immune complexes involving diverse antigens and corresponding antibodies were analyzed for mapping conformational transitions of an antibody before antigen binding, upon antigen binding and after antigen release. Molecular dynamics simulations of the two comprehensive datasets consisting of the antigen-free and antigen-bound structures of the germline antibodies 36-65 and BBE6.12H3 provided mechanistic model of antigen encounter by primary antibodies. While native germline antibodies exhibit substantial mobility in the antigen-combining sites, their antigen-bound states exhibit relatively rigid conformations, even in the absence of the antigen suggesting preservation of the structural state after antigen release. It is proposed that acquired rigidity by a germline antibody upon antigen binding may be the first step in affinity maturation in favor of that antigen.