Codon insertion and deletion functions as a somatic diversification mechanism in human antibody repertoires.

Unlabelled It has been suggested that codon insertion and/or deletion may represent a mechanism that, along with hypermutation, contributes to the affinity maturation of antibodies. We used repertoire cloning to examine human antibodies directed against 3 carbohydrate antigens and 1 protein antigen for the presence of such modifications. We find that both the insertion and deletion of codons occur frequently in antigen-specific responses following vaccination. Codon insertions and deletions were observed most often in the complementarity determining regions, and less frequently in the framework regions, of VH, Vkappa, and Vlambda gene segments, and involved motifs known to be preferred targets of somatic hypermutation. Clonal lineage analysis shows that these events occur through out the course of the somatic maturation of individual antibody clones. We also determined that these alterations of paratope structure have varying effects on the relative affinity of the binding site for its cognate antigen.Reviewers This article was reviewed by Mark Shlomchik, Deborah Dunn-Walters (nominated by Dr. Andrew Macpherson), and Rachel M. Gerstein.Open peer review Reviewed by Mark Shlomchik, Deborah Dunn-Walters (nominated by Dr. Andrew Macpherson), and Rachel M. Gerstein. For the full reviews, please go to the Reviewers' comments section.