Proposed mechanism for conversion of an alloantibody to an autoantibody during somatic hypermutation in an evolving humoral immune response. Blocks depict the antibody-antigen interface. (A; ▲) The polymorphic amino acid that determines an alloantigen and initially induces an alloantibody that recognizes this and adjacent nonpolymorphic residues. (B) By chance, somatic hypermutation (SHM) creates additional mutations (C and D) in the antibody CDR. Mutation C abolishes affinity for the amino acid that determines the alloantigen and mutation D enhances affinity for an adjacent nonpolymorphic amino acid. The resulting autoantibody binds to the same region on the counterpart autologous protein with sufficient affinity to lead to platelet destruction.