More Than Meets the Kappa for Antibody Superantigen Protein L (PpL)
Immunoglobulin superantigens play an important role in affinity purification of antibodies and the microbiota-immune axis at mucosal areas. Based on current understanding, <i>Staphylococcal</i> Protein A (SpA), <i>Streptococcal</i> Protein G (SpG) and <i>Finegoldia</...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Antibodies |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4468/11/1/14 |
| _version_ | 1797447270086475776 |
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| author | Wei-Li Ling Joshua Yi Yeo Yuen-Ling Ng Anil Wipat Samuel Ken-En Gan |
| author_facet | Wei-Li Ling Joshua Yi Yeo Yuen-Ling Ng Anil Wipat Samuel Ken-En Gan |
| author_sort | Wei-Li Ling |
| collection | DOAJ |
| description | Immunoglobulin superantigens play an important role in affinity purification of antibodies and the microbiota-immune axis at mucosal areas. Based on current understanding, <i>Staphylococcal</i> Protein A (SpA), <i>Streptococcal</i> Protein G (SpG) and <i>Finegoldia</i> 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. |
| first_indexed | 2024-03-09T13:53:27Z |
| format | Article |
| id | doaj.art-d3515602ee7145c5b18f8f82230f66e3 |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-03-09T13:53:27Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-d3515602ee7145c5b18f8f82230f66e32023-11-30T20:47:10ZengMDPI AGAntibodies2073-44682022-02-011111410.3390/antib11010014More Than Meets the Kappa for Antibody Superantigen Protein L (PpL)Wei-Li Ling0Joshua Yi Yeo1Yuen-Ling Ng2Anil Wipat3Samuel Ken-En Gan4Antibody & Product Development Laboratory, Experimental Drug Development Centre—Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore 138672, SingaporeAntibody & Product Development Laboratory, Experimental Drug Development Centre—Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore 138672, SingaporeNewcastle Research and Innovation Institute (NewRIIS), Singapore 609607, SingaporeSchool of Computing, Newcastle University, Newcastle upon Tyne NE1 7RU, UKAntibody & Product Development Laboratory, Experimental Drug Development Centre—Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore 138672, SingaporeImmunoglobulin superantigens play an important role in affinity purification of antibodies and the microbiota-immune axis at mucosal areas. Based on current understanding, <i>Staphylococcal</i> Protein A (SpA), <i>Streptococcal</i> Protein G (SpG) and <i>Finegoldia</i> 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.https://www.mdpi.com/2073-4468/11/1/14PertuzumabTrastuzumabIgG1VH familiesVK familiesimmunoglobulin |
| spellingShingle | Wei-Li Ling Joshua Yi Yeo Yuen-Ling Ng Anil Wipat Samuel Ken-En Gan More Than Meets the Kappa for Antibody Superantigen Protein L (PpL) Antibodies Pertuzumab Trastuzumab IgG1 VH families VK families immunoglobulin |
| title | More Than Meets the Kappa for Antibody Superantigen Protein L (PpL) |
| title_full | More Than Meets the Kappa for Antibody Superantigen Protein L (PpL) |
| title_fullStr | More Than Meets the Kappa for Antibody Superantigen Protein L (PpL) |
| title_full_unstemmed | More Than Meets the Kappa for Antibody Superantigen Protein L (PpL) |
| title_short | More Than Meets the Kappa for Antibody Superantigen Protein L (PpL) |
| title_sort | more than meets the kappa for antibody superantigen protein l ppl |
| topic | Pertuzumab Trastuzumab IgG1 VH families VK families immunoglobulin |
| url | https://www.mdpi.com/2073-4468/11/1/14 |
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