If the immune repertoire evolved to be large, random, and somatically generated, then…

The evolution of the somatically generated random combining site repertoire of the “adaptive” immune system depended on the concurrent appearance of a somatic process that sorted the repertoire into anti-self and anti-nonself. Unlike the germline-selected sorting process characteristic of “innate” defense mechanisms, somatic sorting of the repertoire requires that antigens be classified based on their behavior, not on their physical or chemical properties. As specific recognitive combining sites (paratopes) define antigenic determinants (epitopes), the sorting of the repertoire operates epitope-by-epitope. By contrast, the coupling of the paratope to effector function must operate antigen-by-antigen because the response to each epitope on the antigen must be in the same effector class (i.e., coherent). This distinction resolves a long standing debate and provides a basis for analyzing the various models.