Characterization of Porcine Antibodies from Sequence Repertoire and Structural Data

Antibodies possess unique sequence and structural traits that impact how they recognize antigens. While numerous studies have examined porcine antibodies, their repertoire and structural attributes have not been as thoroughly explored compared to other mammalian species. To gain insight into the distinct features of porcine antibodies, this research examined publicly available porcine heavy-chain repertoire sequencing data alongside existing antibody structural information.

The study identified specific amino acids that are more common in porcine antibody framework regions, particularly at the base of the heavy-chain complementarity-determining region 3 (CDR-H3). Arg101 and Glu123 were observed to be closely positioned in available structures, and may play a role in shaping the CDR-H3 conformation at its base.

Additionally, Pro120 was found to assist in maintaining local backbone conformation. The researchers also noted the presence of non-canonical cysteine residues in both framework region 1 and CDR-H3, suggesting that such usage may contribute to the structural diversity within the porcine antibody repertoire. Lastly, the study evaluated the potential for humanizing a porcine antibody by utilizing a human antibody language model.

While the model-guided substitutions increased the human-likeness of the antibody sequence, the resulting sequences did not surpass the T20 scoring threshold. In conclusion, this investigation reveals that porcine antibodies exhibit unique sequence and structural characteristics that could influence the properties of the CDR-H3 region, making it essential to take these factors into account when analyzing and engineering antibodies in the future.