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Front. Immunol. | doi: 10.3389/fimmu.2018.02278

Understanding the significance and implications of antibody numbering and antigen-binding surface/residue definition

 Mathieu Dondelinger1*, Patrice Filée2, Eric Sauvage1,  Birgit Quinting3,  Serge Muyldermans4, Moreno Galleni1 and  Marylène S. Vandevenne1*
  • 1Université de Liège, Belgium
  • 2Centre d’Economie rurale, Belgium
  • 3Haute Ecole Libre Mosane, Belgium
  • 4Vrije Universiteit Brussel, Belgium

Monoclonal antibodies are playing an increasing role in both human and animal health. Different strategies of protein and chemical engineering, including humanization techniques of non-human antibodies were applied successfully to optimize clinical performances of antibodies. Despite the emergence of techniques allowing the development of fully human antibodies such as transgenic Xeno-mice, antibody humanization remains a standard procedure for therapeutic antibodies. An important prerequisite for antibody humanization requires standardized numbering methods to define precisely complementary determining regions (CDR), frameworks and residues from the light and heavy chains that affect the binding affinity and/or specificity of the antibody-antigen interaction. The recently generated deep-sequencing data and the increasing number of solved three-dimensional structures of antibodies from human and non-human origins have led to the emergence of numerous databases. However, these different databases use different numbering conventions and CDR definitions. In addition, the large fluctuation of the variable chain lengths, especially in CDR3 of heavy chains (CDRH3), hardly complicates the comparison and analysis of antibody sequences and the identification of the antigen binding residues.

This review compares and discusses the different numbering schemes and “CDR” definition that were established up to date. Furthermore, it summarizes concepts and strategies used for numbering residues of antibodies and CDR residues identification. Finally, it discusses the importance of specific sets of residues in the binding affinity and/or specificity of immunoglobulins.

Keywords: Numbering schemes, complementary determining regions, Antibody engineering, Antibody humanization, antigen binding residues

Received: 06 Jul 2018; Accepted: 13 Sep 2018.

Edited by:

Marc H. Van Regenmortel, Centre national de la recherche scientifique (CNRS), France

Reviewed by:

Carole Henry, University of Chicago, United States
Neil S. Greenspan, Case Western Reserve University, United States  

Copyright: © 2018 Dondelinger, Filée, Sauvage, Quinting, Muyldermans, Galleni and Vandevenne. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mr. Mathieu Dondelinger, Université de Liège, Liège, 4000, Liège, Belgium, mdondelinger@uliege.be
Dr. Marylène S. Vandevenne, Université de Liège, Liège, 4000, Liège, Belgium, mvandevenne@uliege.be