Investigating the Genetic Basis and Functional Implications of High-Affinity Antibodies Targeting Grass Pollen Allergen Phl p 5
(2024) KIMM05 20242Department of Immunotechnology
- Abstract
- Grass pollen allergens, including Phl p 5 from Phleum pratense, are major triggers of seasonal allergic rhinitis, primarily mediated by IgE antibodies. This study investigates the genetic basis and functional characteristics of IgG1 antibodies targeting Phl p 5, possibly derived from type 2 memory B cells predisposed to IgE switching. Using site-directed mutagenesis, we analyzed variants of a high-affinity IgG1 antibody (212579), focusing on allele-specific mutations and reverse mutations toward an unmutated precursor.
Binding kinetics, thermal stability, and structural integrity were assessed via ELISA, SPR, NanoDSF, and FidaNeo. Variants with T40N, a germline-encoded mutation, demonstrated enhanced thermal stability, indicating a... (More) - Grass pollen allergens, including Phl p 5 from Phleum pratense, are major triggers of seasonal allergic rhinitis, primarily mediated by IgE antibodies. This study investigates the genetic basis and functional characteristics of IgG1 antibodies targeting Phl p 5, possibly derived from type 2 memory B cells predisposed to IgE switching. Using site-directed mutagenesis, we analyzed variants of a high-affinity IgG1 antibody (212579), focusing on allele-specific mutations and reverse mutations toward an unmutated precursor.
Binding kinetics, thermal stability, and structural integrity were assessed via ELISA, SPR, NanoDSF, and FidaNeo. Variants with T40N, a germline-encoded mutation, demonstrated enhanced thermal stability, indicating a trade-off between binding affinity and structural robustness. The IGHV3-48*03 allele, distinguished by unique residues E38 and G62, conferred high binding affinity, with substitutions E38S reducing allergen recognition. Combined heavy and light chain mutations further revealed additive impacts on stability and flexibility under thermal stress.
These findings underscore the critical role of allelic diversity and specific mutations in shaping antibody functionality. IGHV3-48*03 was uniquely capable of generating high-affinity binders to Phl p 5, emphasizing its relevance in allergen-specific immune responses. This study provides insights into allergen-specific IgG1 antibodies, with implications for diagnostics and therapeutic strategies. (Less) - Popular Abstract
- Decoding Grass Pollen Allergies: How Antibodies and Genetics Shape Our Immune Response
Every spring, millions suffer from sneezing, itchy eyes, and other symptoms of grass pollen allergies. Could decoding the genetics of our immune system provide a path to relief?
Grass pollen allergies affect over 30% of the global population, with a specific protein in Timothy grass pollen, Phl p 5, acting as a major trigger. While IgE antibodies are primarily responsible for these reactions, other antibodies like IgG1 may hold valuable clues to understanding and managing allergies. This study focused on IgG1, a type of antibody that could offer insights into how our immune system targets allergens and how minor genetic variations shape its... (More) - Decoding Grass Pollen Allergies: How Antibodies and Genetics Shape Our Immune Response
Every spring, millions suffer from sneezing, itchy eyes, and other symptoms of grass pollen allergies. Could decoding the genetics of our immune system provide a path to relief?
Grass pollen allergies affect over 30% of the global population, with a specific protein in Timothy grass pollen, Phl p 5, acting as a major trigger. While IgE antibodies are primarily responsible for these reactions, other antibodies like IgG1 may hold valuable clues to understanding and managing allergies. This study focused on IgG1, a type of antibody that could offer insights into how our immune system targets allergens and how minor genetic variations shape its effectiveness.
Antibodies are proteins produced by immune cells to recognize and neutralize harmful substances. IgG1 antibodies against Phl p 5, which may act as precursors to IgE, were studied to investigate how small genetic changes influence their ability to bind allergens and remain stable. Through experiments using advanced laboratory techniques, this research explored how these modifications affect the antibodies’ performance.
Certain genetic variations in antibody-producing genes were shown to enhance the ability of IgG1 antibodies to bind allergens like Phl p 5 strongly. However, this improved binding sometimes came at a cost: reduced structural stability. This trade-off highlights the complexity of the immune response, where genetic changes can both enhance and compromise antibody functionality.
Even the “unmutated precursor” form of the antibody, a version closer to its natural state, demonstrated significant effectiveness in binding Phl p 5. This finding underscores the remarkable adaptability of our immune system, even without extensive genetic fine-tuning.
Understanding how antibodies interact with allergens at a molecular level can pave the way for improved allergy diagnostics and treatments. For instance, therapies mimicking high-performing antibodies could reduce allergic reactions or even prevent them. By decoding how genetic variations shape immune responses, this research contributes to developing more personalized approaches to allergy management, potentially improving the lives of millions. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9178882
- author
- Essén, Mattias LU
- supervisor
- organization
- course
- KIMM05 20242
- year
- 2024
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9178882
- date added to LUP
- 2025-01-08 13:24:15
- date last changed
- 2025-01-08 13:24:15
@misc{9178882,
abstract = {{Grass pollen allergens, including Phl p 5 from Phleum pratense, are major triggers of seasonal allergic rhinitis, primarily mediated by IgE antibodies. This study investigates the genetic basis and functional characteristics of IgG1 antibodies targeting Phl p 5, possibly derived from type 2 memory B cells predisposed to IgE switching. Using site-directed mutagenesis, we analyzed variants of a high-affinity IgG1 antibody (212579), focusing on allele-specific mutations and reverse mutations toward an unmutated precursor.
Binding kinetics, thermal stability, and structural integrity were assessed via ELISA, SPR, NanoDSF, and FidaNeo. Variants with T40N, a germline-encoded mutation, demonstrated enhanced thermal stability, indicating a trade-off between binding affinity and structural robustness. The IGHV3-48*03 allele, distinguished by unique residues E38 and G62, conferred high binding affinity, with substitutions E38S reducing allergen recognition. Combined heavy and light chain mutations further revealed additive impacts on stability and flexibility under thermal stress.
These findings underscore the critical role of allelic diversity and specific mutations in shaping antibody functionality. IGHV3-48*03 was uniquely capable of generating high-affinity binders to Phl p 5, emphasizing its relevance in allergen-specific immune responses. This study provides insights into allergen-specific IgG1 antibodies, with implications for diagnostics and therapeutic strategies.}},
author = {{Essén, Mattias}},
language = {{eng}},
note = {{Student Paper}},
title = {{Investigating the Genetic Basis and Functional Implications of High-Affinity Antibodies Targeting Grass Pollen Allergen Phl p 5}},
year = {{2024}},
}