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Related Concept Videos

Antibody Structure01:10

Antibody Structure

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Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
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What is Natural Selection?01:32

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Natural selection is an evolutionary process in which individuals with survival-promoting traits reproduce at higher rates. These favorable traits become more common within a population or species. Naturally selected traits initially arise via random genetic mutations. In order for selection to occur, there must be variation within a population, the trait controlling the variation must be heritable, and there must be an evolutionary advantage for variation in the trait.
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Types of Selection01:46

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Natural selection influences the frequencies of particular alleles and phenotypes within populations in several different ways. Primarily, natural selection can be directional, stabilizing, or disruptive. Directional selection favors one extreme trait and shifts the population towards that phenotype while selecting against individuals displaying alternate traits. Stabilizing selection favors an intermediate trait with a narrow range of variation. Deviation from the optimal phenotype towards an...
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When the fitness of a trait is influenced by how common it is (i.e., its frequency) relative to different traits within a population, this is referred to as frequency-dependent selection. Frequency-dependent selection may occur between species or within a single species. This type of selection can either be positive—with more common phenotypes having higher fitness—or negative, with rarer phenotypes conferring increased fitness.
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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.
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Scalable High Throughput Selection From Phage-displayed Synthetic Antibody Libraries
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Human Antibody Bispecifics through Phage Display Selection.

Ansha Luthra1,2, David B Langley1, Peter Schofield1,2

  • 1Garvan Institute of Medical Research , 384 Victoria Road , Darlinghurst, Sydney , New South Wales 2010 , Australia.

Biochemistry
|March 23, 2019
PubMed
Summary

We created a new method to generate human bispecific antibodies. This approach uses phage display to select antibody chains that correctly assemble, preventing mispairing for efficient bispecific antibody production.

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Area of Science:

  • Immunotechnology
  • Protein Engineering
  • Antibody Engineering

Background:

  • Bispecific antibodies offer enhanced therapeutic potential by engaging multiple targets simultaneously.
  • Current methods for generating bispecific antibodies can be complex and prone to mispairing of antibody chains.
  • Developing strategies for efficient and specific assembly of bispecific antibodies is crucial for their clinical application.

Purpose of the Study:

  • To develop a novel repertoire approach for generating human antibody bispecifics.
  • To identify mutations that prevent heavy/light chain mispairing in bispecific antibody formats.
  • To enable the selection of antibody chains that autonomously assemble into functional bispecific antibodies.

Main Methods:

  • Utilized phage display selection to identify antibody heavy chains.
  • Employed a competitor light chain during selection to identify chains with specific pairing properties.
  • Incorporated an affinity handle on the cognate light chain to guide proper assembly.
  • Screened for mutations that abrogate heavy/light chain mispairing.

Main Results:

  • Successfully developed a repertoire approach for human bispecific antibody generation.
  • Identified specific mutations that effectively prevent heavy/light chain mispairing.
  • Demonstrated that selected antibody chains autonomously assemble into bispecific formats.
  • The strategy allows for the selection of stable and functional bispecific antibodies.

Conclusions:

  • The developed repertoire approach provides an efficient method for producing human bispecific antibodies.
  • Preventing heavy/light chain mispairing through targeted mutations is key to autonomous bispecific assembly.
  • This strategy facilitates the generation of diverse and specific bispecific antibody repertoires for therapeutic development.