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Updated: May 12, 2026
15:07
VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig™) molecule
Clarissa G Jakob1, Rohinton Edalji2, Russell A Judge1
1Department of Structural Biology; AbbVie Inc.; North Chicago, IL USA.
Mabs
|April 4, 2013
Summary
Dual-variable domain immunoglobulin (DVD-Ig™) molecules are flexible tetravalent biologics. Structural analysis reveals how DVD-Ig™ can bind four antigens, aiding future bispecific biologic design.
Area of Science:
- Biotechnology
- Immunology
- Structural Biology
Background:
- Bispecific antibodies offer targeted immunotherapeutics by engaging multiple disease pathways.
- The dual-variable domain immunoglobulin (DVD-Ig™) format creates tetravalent IgG-like molecules by linking antibody variable domains.
Purpose of the Study:
- To elucidate the structural basis for the functionality of the DVD-Ig™ format.
- To understand how the inner variable domain of DVD-Ig™ retains binding capacity.
Main Methods:
- X-ray crystallography was used to determine the structure of an interleukin (IL)12-IL18 DVD-Ig™ Fab (DFab) fragment.
- The structure captured the DFab with IL18 bound to the inner variable domain.
Main Results:
- The crystal structure revealed the significant flexibility inherent in the DVD-Ig™ molecule.
- The inner variable domain demonstrated retained functionality, enabling simultaneous binding to multiple antigens.
- The DVD-Ig™ format was shown to potentially bind up to four antigens.
Conclusions:
- Understanding the structural flexibility and functional retention of DVD-Ig™ is crucial for its rational design.
- This knowledge can inform the development of improved bispecific and multispecific biologics.
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