Towards a quantitative model of immunogenicity: Counting pathways in sequence space

One of the fundamental aims of structural biology is the identification of high-affinity ligands for arbitrary receptors. The maturation of the antibo dy repertoire elegantly and robustly solves this problem through an evoluti onary mechanism comprising repeated cycles of mutation and preferential rep lication. To understand better the limitations and biases of this process, we developed an interpretation of antibody maturation within the framework of sequence space and fitness landscapes. Several well-described phenomena can be directly derived from this framework, and new predictions can be mad e. Ultimately, this reconceptualization of the clonal selection process sug gests a quantitative, testable model of immunogenicity. (C) 2000 Academic P ress.