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Published on: April 20, 2021
Germline VH/VL pairing in antibodies
Narayan Jayaram1, Pallab Bhowmick, Andrew C R Martin
1Institute of Structural and Molecular Biology, Division of Biosciences, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
Protein Engineering, Design & Selection : PEDS
|July 18, 2012
Summary
Antibody heavy and light chain pairing is not entirely random. Germline gene segments show specific pairing preferences, impacting biopharmaceutical antibody stability.
Area of Science:
- Immunology
- Biotechnology
- Structural Biology
Background:
- Antibodies are crucial for adaptive immunity and biopharmaceuticals.
- Antibody diversity arises from heavy and light chain pairing.
- Previous research suggested random germline V(H)/V(L) pairing.
Purpose of the Study:
- To investigate germline V(H)/V(L) pairing preferences.
- To compare human and mouse germline pairing preferences.
- To assess the implications for biopharmaceutical antibody development.
Main Methods:
- Selected paired antibody sequences from the KabatMan database (human and mouse).
- Mapped paired sequences to their germline gene segments.
- Identified equivalent human and mouse gene families for comparison.
Main Results:
- Germline V(H)/V(L) pairing preferences were observed.
- Preferences were specific to a subset of germline gene segments.
- Other gene segments exhibited promiscuous pairing behavior.
- Human and mouse germline pairing preferences were compared.
Conclusions:
- Germline pairing is not completely random, with specific preferences existing.
- Understanding these preferences can inform the design of more stable antibodies.
- This research has potential applications in biopharmaceutical antibody engineering.
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