A potential antibody repertoire diversification mechanism through tyrosine sulfation for biotherapeutics engineering and production

The diversity of three hypervariable loops in antibody heavy chain and light chain, termed the complementarity-determining regions (CDRs), defines antibody's binding affinity and specificity owing to the direct contact between the CDRs and antigens. These CDR regions typically contain tyrosine (Tyr) residues that are known to engage in both nonpolar and pi stacking interaction with antigens through their complementary aromatic ring side chains. Nearly two decades ago, sulfotyrosine residue (sTyr), a negatively charged Tyr formed by Golgi-localized membrane-bound tyrosylprotein sulfotransferases during protein trafficking, were also found in the CDR regions and shown to play an important role in modulating antibody-antigen interaction. This breakthrough finding demonstrated that antibody repertoire could be further diversified through post-translational modifications, in addition to the conventional genetic recombination. This review article summarizes the current advances in the understanding of the Tyr-sulfation modification mechanism and its application in potentiating protein-protein interaction for antibody engineering and production. Challenges and opportunities are also discussed.

Automated summary

The diversity of antibody's binding affinity and specificity is determined by the complementarity-determining regions (CDRs), which are the three hypervariable loops in the antibody heavy chain and light chain. Tyrosine residues in these CDR regions play a crucial role in the interaction between antibodies and antigens. The sulfation modification of tyrosine residues further enhances the diversity of the antibody repertoire. This review article provides an overview of the mechanism of tyrosine sulfation modification and its application in antibody engineering and production, while also discussing the challenges and opportunities in this field.