Antibody promiscuity: Understanding the paradigm shift in antigen recognition

Affinity maturation is associated with reduced malleability of the paratope that optimizes an antibody to bind to the bonafide antigen with high specificity and affinity. However, it has been illustrated that mature antibodies tend to exhibit promiscuity despite acquisition of a relatively rigid binding pocket. Such an attribute is contrary to the established paradigm of specificity in antigen recognition. In this review, an explicit dissection of the underlying mechanisms fostering such versatility in mature antibodies has been done. Polyspecificity is essentially achieved by undergoing minimal structural rearrangement at the paratope complemented with plasticity in interaction with antigen. Besides, the structural invariance of the antigen across species could modulate mature antibody specificity. Polyreactivity has been well documented for germline antibodies as broad spectrum antibody repertoire amplification is primarily governed by recombination event of the genetic machinery, which is further expanded at the structural and functional level of interaction. Degenerate specificity in antigen recognition obviates the need to produce distinct antibody for every incoming epitope.