More Than Meets the Kappa for Antibody Superantigen Protein L (PpL)

Antibodies

Wei-Li Ling¹  Joshua Yi Yeo¹  Samuel Ken-En Gan¹  Yuen-Ling Ng²  Anil Wipat³ 

[1] Antibody & Product Development Laboratory, Experimental Drug Development Centre—Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore 138672, Singapore;Newcastle Research and Innovation Institute (NewRIIS), Singapore 609607, Singapore;School of Computing, Newcastle University, Newcastle upon Tyne NE1 7RU, UK;

关键词: Pertuzumab;    Trastuzumab;    IgG1;    VH families;    VK families;    immunoglobulin;   

DOI  :  10.3390/antib11010014

来源: DOAJ

【 摘 要 】

Immunoglobulin superantigens play an important role in affinity purification of antibodies and the microbiota-immune axis at mucosal areas. Based on current understanding, Staphylococcal Protein A (SpA), Streptococcal Protein G (SpG) and Finegoldia Protein L (PpL) are thought to only bind specific regions of human antibodies, allowing for selective purification of antibody isotypes and chains. Clinically, these superantigens are often classified as toxins and increase the virulence of the producing pathogen through unspecific interactions with immune proteins. To perform an in-depth interaction study of these three superantigens with antibodies, bio-layer interferometry (BLI) measurements of their interactions with a permutation panel of 63 IgG1 variants of Pertuzumab and Trastuzumab CDRs grafted to the six human Vκ and seven human VH region families were tested. Through this holistic and systemic analysis of IgG1 variants with various antibody regions modified, comparisons revealed novel PpL–antibody interactions influenced by other non-canonical antibody known light-chain framework regions, whereas SpA and SpG showed relatively consistent interactions. These findings have implications on PpL-based affinity antibody purification and design that can guide the engineering and understanding of PpL-based microbiota-immune effects.

【 授权许可】

Unknown