Variable Lymphocyte Receptors for Jawless Vertebrate Immunity
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Solution Overview
Problem
The immune systems of jawless vertebrates, such as lampreys and hagfish, lack identified immunoglobulin (Ig), T cell receptor (TCR), and major histocompatibility complex (MHC) genes, hindering the understanding and development of adaptive immune responses.
Innovation Solution
Discovery of novel lymphocyte receptors and nucleic acids in lampreys, specifically variable lymphocyte receptors (VLRs), which undergo somatic rearrangement and are capable of adaptive immunity, including polypeptides with leucine-rich repeats (LRRs) and associated nucleic acids for therapeutic, diagnostic, and purification methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immune system models based on Ig, TCR, and MHC genes are applied to jawless vertebrates, then the understanding of adaptive immunity is limited, but the complexity of the immune system model remains high due to the absence of these genes
Solution Approach 1:
The patent creates a functional copy of the adaptive immune system mechanism by discovering VLRs that perform antibody-like functions without requiring Ig genes. The VLRs are composed of leucine-rich repeats that can be rearranged to generate diversity, copying the essential function of conventional B-cell receptors while using a different molecular architecture suitable for jawless vertebrates.
Solution Approach 2:
The patent fundamentally changes the genetic parameter from Ig/TCR/MHC-based systems to a VLR-based system using leucine-rich repeat modules. This parameter change allows the immune system to achieve diversity through somatic rearrangement of LRR modules rather than through V(D)J recombination, resolving the contradiction by adapting the immune model to the actual genetic capabilities of jawless vertebrates.
2Adaptability or versatility
If VLRs with somatic rearrangement capability are discovered in lampreys, then adaptive immune diversity is achieved, but the structural complexity of the receptor system increases
Solution Approach 1:
The VLR system divides the receptor structure into modular leucine-rich repeat units that can be independently arranged and recombined. Each LRR module is a discrete functional unit that contributes to antigen binding, and these modules can be segmented and rearranged through somatic recombination to generate diverse receptor specificities without requiring an overly complex overall structure.
Solution Approach 2:
The patent resolves structural complexity by transitioning from the conventional three-dimensional V(D)J recombination mechanism to a modular assembly approach where LRR units are arranged in a standardized beta-sheet configuration. This dimensional standardization of the modular units allows for diversity in sequence composition while maintaining structural simplicity and predictability.
Data Source
AI summary
Disclosed are compositions and methods related to variable lymphocyte receptors (VLRs).