Understanding the Significance and Implications of Antibody Numbering and Antigen-Binding Surface/Residue Definition

@article{Dondelinger2018UnderstandingTS,
  title={Understanding the Significance and Implications of Antibody Numbering and Antigen-Binding Surface/Residue Definition},
  author={Mathieu Dondelinger and Patrice Fil{\'e}e and Eric Sauvage and Birgit Quinting and Serge Muyldermans and Moreno Galleni and Maryl{\'e}ne Vandevenne},
  journal={Frontiers in Immunology},
  year={2018},
  volume={9}
}
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… 

Figures from this paper

Humanization of Chicken‐Derived scFv Using Yeast Surface Display and NGS Data Mining
TLDR
Next‐generation sequencing discloses humanized antibody variants with restored affinity and improved protein characteristics compared to the parental chicken antibodies, and new insights into the importance of antibody format are given during the humanization process.
Sagacity in antibody humanization for therapeutics, diagnostics and research purposes: considerations of antibody elements and their roles
TLDR
Considerations such as better antibody localization, avoidance of unspecific interactions to superantigens and the tailoring of antibody dependent triggering of immune responses, the antibody persistence on cells, can all be preemptively considered through a holistic sagacious approach, allowing for better outcomes in therapy and for research and diagnostic purposes.
Characterization of the specific interactions between nanoparticles and proteins at residue-resolution by alanine scanning mutagenesis.
TLDR
Experimental results reveal that the key residues of the CDR peptides for the specific interactions between the two Goldbodies and the corresponding antigens are exactly the same as that in the natural antibodies, thus proving that the correct conformations of theCDRs of natural antibodies have been successfully reconstructed on AuNPs.
Conformational changes in a Vernier zone region: Implications for antibody dual specificity
TLDR
It was showed that a particular region of clustered Vernier zone residues might play key roles in gaining dual specificity, and a significant structural change and consequently close contact formation between LV4‐LCDR1 loops of derived dual‐specific antibodies.
Computational approaches to therapeutic antibody design: established methods and emerging trends
TLDR
A structured overview of available databases, methods and emerging trends in computational antibody analysis are presented and contextualize them towards the engineering of candidate antibody therapeutics.
Affinity maturation: highlights in the application of in vitro strategies for the directed evolution of antibodies
TLDR
This article discusses recent efforts in the affinity maturation of a difficult antibody lineage using an unbiased approach, which sought to explore a larger sequence space through the application of DNA recombination and shuffling techniques across the entire antibody region and selections using ribosome display.
Antibodies targeting enzyme inhibition as potential tools for research and drug development
TLDR
The molecular mechanisms and recent trends by which antibodies inhibit the catalytic activity of enzymes are reviewed and examples of how specific antibodies can be useful for the neutralization of biologically active molecules are provided.
Benchmarking immunoinformatic tools for the analysis of antibody repertoire sequences
Abstract Summary Antibody repertoires reveal insights into the biology of the adaptive immune system and empower diagnostics and therapeutics. There are currently multiple tools available for the
Designing and generating a single-chain fragment variable (scFv) antibody against IL2Rα (CD25): An in silico and in vitro study
TLDR
This work provides a theoretical and experimental basis for production of an anti-CD25 scFv, which may be applied for various malignant disorders and autoimmune diseases.
...
...

References

SHOWING 1-10 OF 105 REFERENCES
Development of Scoring Functions for Antibody Sequence Assessment and Optimization
TLDR
It is demonstrated that, using the developed potentials, humanization of an antibody can be described as a simple mathematical optimization problem and that the in-silico generated framework variants closely resemble native sequences in terms of predicted immunogenicity.
Conservation and diversity in the ultralong third heavy-chain complementarity-determining region of bovine antibodies
TLDR
Crystal structures of three new bovine Fab fragments are determined to decipher the conserved and variable features of ultralong CDR H3s that lead to diversity in antigen recognition and may inform efforts in antibody engineering.
Antibody framework residues affecting the conformation of the hypervariable loops.
Prediction of site-specific interactions in antibody-antigen complexes: the proABC method and server
TLDR
This article presents a method to identify, on the basis of the antibody sequence alone, which residues of an antibody directly interact with its cognate antigen, and is implemented as a free and easy-to-use server, named prediction of Antibody Contacts.
VH-VL orientation prediction for antibody humanization candidate selection: A case study
TLDR
This work proposes a novel approach that selects acceptor frameworks such that the relative orientation of the 2 variable domains in 3D space, and thereby the geometry of the antigen-binding site, is conserved throughout the process of humanization.
Comparison of surface accessible residues in human and murine immunoglobulin Fv domains. Implication for humanization of murine antibodies.
TLDR
Using these patterns of human and murine surface residues a novel method for the "humanization" of murine antibodies has been developed and tested and suggests that the surfaces of V-regions are at least as well conserved as the core framework sequences.
Replacing the complementarity-determining regions in a human antibody with those from a mouse
TLDR
This work substituted the CDRs from the heavy-chain variable region of mouse antibody B1–8, which binds the hapten NP-cap, for the corresponding CDRs of a human myeloma protein, to determine whether the antigen-binding site could be transplanted from one framework to another by grafting theCDRs.
Aligning, analyzing, and visualizing sequences for antibody engineering: Automated recognition of immunoglobulin variable region features
The analysis and comparison of large numbers of immunoglobulin (Ig) sequences that arise during an antibody selection campaign can be time‐consuming and tedious. Typically, the identification and
...
...