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Antibody Actions

Antibody Actions

Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...

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Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia

Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia

Published on: November 9, 2018

Specific amyloid β clearance by a catalytic antibody construct.

Stephanie A Planque¹, Yasuhiro Nishiyama¹, Sari Sonoda¹

¹From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.

The Journal of Biological Chemistry

|March 1, 2015

Summary

Researchers engineered a novel catalytic antibody (catabody) from innate immunity principles. This catabody effectively clears amyloid beta (Aβ) in a mouse model of Alzheimer disease without adverse effects.

Keywords:

Alzheimer Disease Amyloid-β (Abeta)Antibody Engineering Catalytic Antibodies Enzyme Catalysis Immunotherapy Innate Immunity Light Chain Variable Domain Neurotoxicity

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Area of Science:

Immunology
Neuroscience
Biochemistry

Background:

Classical immunization fails to produce catalytic antibodies (catabodies).
The innate antibody repertoire is a potential source for catabodies.
Amyloid beta (Aβ) is implicated in Alzheimer disease pathogenesis.

Purpose of the Study:

To engineer and characterize a catabody with specificity for amyloid beta (Aβ).
To evaluate the Aβ-clearing efficacy and therapeutic potential of the engineered catabody.

Main Methods:

Engineering a catabody construct based on innate immunity principles.
Assessing catabody specificity and catalytic activity against Aβ.
Evaluating the catabody's effect on preformed Aβ aggregates and Aβ aggregation.
Administering the catabody intravenously in a mouse model of Alzheimer disease.

Main Results:

The engineered catabody recognized and rapidly hydrolyzed the Aβ C terminus.
The catabody showed high specificity, with no reactivity to related proteins or off-target sequences.
It effectively dissolved preformed Aβ aggregates and inhibited further aggregation.
Intravenous administration reduced brain Aβ deposits in a mouse Alzheimer disease model without inducing inflammation or hemorrhage.

Conclusions:

Specific Aβ hydrolysis is a potential innate immune function.
Engineered catabodies derived from innate immunity principles offer a promising therapeutic strategy for Aβ removal in Alzheimer disease.
This approach demonstrates potential for safe and effective Aβ clearance.