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 antibody repertoire elegantly and robustly solves this problem through an evolutionary mechanism comprising repeated cycles of mutation and preferential replication. 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 made. Ultimately, this reconceptualization of the clonal selection process suggests a quantitative, testable model of immunogenicity.
Chang
T Y
TY
Department of Pathology and Laboratory Medicine, University of Rochester, NY 14642, USA. tylis_chang@umc.rochester.edu
D000906:Antibodies / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D018448:Models, Immunological; D009154:Mutation; D018029:Rho(D) Immune Globulin / Q000276:immunology
D000906:Antibodies; D018029:Rho(D) Immune Globulin