Heterogeneous antigen recognition behavior of induced polyspecific antibodies

► Agents with different chemical nature can reveal the hidden polyspecificity in pooled IgG. ► IgG exposed to different agents have different pattern of antigen reactivity. ► Recognition of unrelated proteins by IgG exposed to a polyspecificity-inducing agent, is governed by similar mechanism Polyspecific antibodies represent a significant fraction of the antibody repertoires in healthy animals and humans. Interestingly, certain antibodies only acquire a polyspecific antigen-binding behavior after exposure to protein-modifying conditions, such as those found at inflammation sites, or used in small- and large-scale immunoglobulin purification. This phenomenon is referred to as “criptic polyspecificity”. In the present study, we compare the potential of different chemical agents to induce IgG polyspecificity. Depending on the treatment used, quantitative and qualitative differences in the recognition of individual antigens from a standard panel were observed. Antibodies with cryptic polyspecificity utilized common mechanisms for the recognition of structurally unrelated antigens when exposed to a particular inductor of polyspecificity. Our study contributes to the understanding of the mechanisms underlying the cryptic polyspecificity.