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Structural insights into the evolution of the adaptive immune system
Lu Deng1, Ming Luo, Alejandro Velikovsky
1Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Annual Review of Biophysics
|March 5, 2013
Summary
Jawless vertebrates evolved unique variable lymphocyte receptors (VLRs) from leucine-rich repeats (LRRs) for adaptive immunity. These LRR-based VLRs exhibit comparable antigen recognition to jawed vertebrate antibodies and T cell receptors (TCRs).
Area of Science:
- Immunology
- Evolutionary Biology
- Structural Biology
Background:
- Adaptive immunity relies on diverse antigen receptors, like antibodies and T cell receptors (TCRs) in jawed vertebrates, generated via somatic recombination.
- These receptors are built from immunoglobulin (Ig) domains with hypervariable loops for antigen binding.
- Jawless vertebrates possess distinct adaptive immune receptors called variable lymphocyte receptors (VLRs).
Purpose of the Study:
- To investigate the structural basis of antigen recognition by VLRs in jawless vertebrates.
- To compare the molecular mechanisms of VLRs with Ig-based receptors in jawed vertebrates.
- To understand the evolutionary convergence of adaptive immunity scaffolds.
Main Methods:
- Structural studies of VLRs.
- Analysis of VLR-antigen binding interactions.
- Comparative analysis of receptor scaffolds (LRR vs. Ig domains).
Main Results:
- VLRs are constructed from leucine-rich repeat (LRR) modules.
- LRR-based VLRs bind antigens via their concave surface and a hypervariable loop in the C-terminal LRR capping module.
- Jawless vertebrates utilize the LRR scaffold for antigen recognition with comparable affinity and specificity to Ig-based receptors.
Conclusions:
- Jawless vertebrates exhibit a remarkable example of convergent evolution in adaptive immunity.
- The LRR scaffold has evolved independently to mediate adaptive immune responses, mirroring the function of Ig-based receptors.
- VLRs represent an alternative, yet functionally equivalent, system for adaptive immunity in vertebrates.
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