A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodies
The human immune system uses antibodies to neutralize foreign antigens. They are composed of heavy and light chains, both with constant and variable regions. The variable region has six hypervariable loops, also known as complementary-determining regions (CDRs) that determine antibody diversity and...
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Taylor & Francis Group
2023-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2023.2268255 |
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| author | Oscar Mejias-Gomez Andreas V. Madsen Kerstin Skovgaard Lasse E. Pedersen J. Preben Morth Timothy P. Jenkins Peter Kristensen Steffen Goletz |
| author_facet | Oscar Mejias-Gomez Andreas V. Madsen Kerstin Skovgaard Lasse E. Pedersen J. Preben Morth Timothy P. Jenkins Peter Kristensen Steffen Goletz |
| author_sort | Oscar Mejias-Gomez |
| collection | DOAJ |
| description | The human immune system uses antibodies to neutralize foreign antigens. They are composed of heavy and light chains, both with constant and variable regions. The variable region has six hypervariable loops, also known as complementary-determining regions (CDRs) that determine antibody diversity and antigen specificity. Knowledge of their significance, and certain residues present in these areas, is vital for antibody therapeutics development. This study includes an analysis of more than 11,000 human antibody sequences from the International Immunogenetics information system (IMGT). The analysis included parameters such as length distribution, overall amino acid diversity, amino acid frequency per CDR and residue position within antibody chains. Overall, our findings confirm existing knowledge, such as CDRH3‘s high length diversity and amino acid variability, increased aromatic residue usage, particularly tyrosine, charged and polar residues like aspartic acid, serine, and the flexible residue glycine. Specific residue positions within each CDR influence these occurrences, implying a unique amino acid type distribution pattern. We compared amino acid type usage in CDRs and non-CDR regions, both in globular and transmembrane proteins, which revealed distinguishing features, such as increased frequency of tyrosine, serine, aspartic acid, and arginine. These findings should prove useful for future optimization, improvement of affinity, synthetic antibody library design, or the creation of antibodies de-novo in silico. |
| format | Article |
| id | doaj-art-457ebf9018dd4c70bbe8e1d0e7fa743e |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-457ebf9018dd4c70bbe8e1d0e7fa743e2025-08-20T03:25:53ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2023.2268255A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodiesOscar Mejias-Gomez0Andreas V. Madsen1Kerstin Skovgaard2Lasse E. Pedersen3J. Preben Morth4Timothy P. Jenkins5Peter Kristensen6Steffen Goletz7Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkDepartment of Chemistry and Bioscience, Aalborg University, Aalborg, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkThe human immune system uses antibodies to neutralize foreign antigens. They are composed of heavy and light chains, both with constant and variable regions. The variable region has six hypervariable loops, also known as complementary-determining regions (CDRs) that determine antibody diversity and antigen specificity. Knowledge of their significance, and certain residues present in these areas, is vital for antibody therapeutics development. This study includes an analysis of more than 11,000 human antibody sequences from the International Immunogenetics information system (IMGT). The analysis included parameters such as length distribution, overall amino acid diversity, amino acid frequency per CDR and residue position within antibody chains. Overall, our findings confirm existing knowledge, such as CDRH3‘s high length diversity and amino acid variability, increased aromatic residue usage, particularly tyrosine, charged and polar residues like aspartic acid, serine, and the flexible residue glycine. Specific residue positions within each CDR influence these occurrences, implying a unique amino acid type distribution pattern. We compared amino acid type usage in CDRs and non-CDR regions, both in globular and transmembrane proteins, which revealed distinguishing features, such as increased frequency of tyrosine, serine, aspartic acid, and arginine. These findings should prove useful for future optimization, improvement of affinity, synthetic antibody library design, or the creation of antibodies de-novo in silico.https://www.tandfonline.com/doi/10.1080/19420862.2023.2268255Amino acid diversityantibodies/immunoglobulinsantibody sequencingantibody therapeutics developmentantibody-antigen complexesComplementary-Determining Regions (CDRs) |
| spellingShingle | Oscar Mejias-Gomez Andreas V. Madsen Kerstin Skovgaard Lasse E. Pedersen J. Preben Morth Timothy P. Jenkins Peter Kristensen Steffen Goletz A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodies mAbs Amino acid diversity antibodies/immunoglobulins antibody sequencing antibody therapeutics development antibody-antigen complexes Complementary-Determining Regions (CDRs) |
| title | A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodies |
| title_full | A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodies |
| title_fullStr | A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodies |
| title_full_unstemmed | A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodies |
| title_short | A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodies |
| title_sort | window into the human immune system comprehensive characterization of the complexity of antibody complementary determining regions in functional antibodies |
| topic | Amino acid diversity antibodies/immunoglobulins antibody sequencing antibody therapeutics development antibody-antigen complexes Complementary-Determining Regions (CDRs) |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2023.2268255 |
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