Antibody Polyreactivity: A Challenger of Immune Paradigms

Polyreactivity refers to the ability of antibodies to bind multiple unrelated antigens, encompassing polyspecificity and promiscuity. Here, we discuss the diverse molecular mechanisms underlying polyreactivity, including conformational dynamics, sequence‐ and structural characteristics of antigen‐binding sites. The importance of polyreactive antibodies in immune defence and immune homeostasis is highlighted as well as their potential pathological consequences. Polyreactivity is seen as a continuum rather than a discrete property so that ultimately all antibodies possess some degree of polyreactivity. The challenges in defining antibody specificity are examined, and a shift towards quantitative thinking in antibody research is suggested. This would foster the adoption of novel methodologies to study complex antibody–antigen interactions at a systems level. Finally, the deeper understanding of polyreactivity's potential implications for the current antibody paradigm is critically evaluated.