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Related Concept Videos

Antibody Structure01:10

Antibody Structure

Overview
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
Antibodies consist of four polypeptide chains: two identical heavy...
Antibody Structure01:10

Antibody Structure

Overview
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
Antibodies consist of four polypeptide chains: two identical heavy...
Hybridoma Technology01:31

Hybridoma Technology

Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
Commonly used fusion techniques — electroporation, polyethylene glycol...
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Antibody Structure and Classes01:25

Antibody Structure and Classes

Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
Humoral Immune Responses01:36

Humoral Immune Responses

Overview

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Related Experiment Video

Updated: May 11, 2026

Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood
13:14

Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood

Published on: February 6, 2018

Human germline antibody gene segments encode polyspecific antibodies.

Jordan R Willis1, Bryan S Briney, Samuel L DeLuca

  • 1Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, USA.

Plos Computational Biology
|May 3, 2013
PubMed
Summary

Germline antibodies exhibit inherent polyspecificity due to structural flexibility. Computational redesign revealed that germline sequences, not mature ones, enable binding to multiple antigens, reversing natural antibody maturation in silico.

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Last Updated: May 11, 2026

Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood
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Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood

Published on: February 6, 2018

Identification of Mouse and Human Antibody Repertoires by Next-Generation Sequencing
08:51

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Published on: March 15, 2019

Generation of Murine Monoclonal Antibodies by Hybridoma Technology
09:42

Generation of Murine Monoclonal Antibodies by Hybridoma Technology

Published on: January 2, 2017

Area of Science:

  • Immunology
  • Computational Biology
  • Structural Biology

Background:

  • Antibodies possess structural flexibility enabling broad antigen recognition.
  • Somatic mutations enhance antibody affinity and specificity during immune responses.
  • Germline antibodies are hypothesized to be inherently polyspecific.

Purpose of the Study:

  • To investigate if germline gene-encoded antibodies are optimal for polyspecificity.
  • To computationally determine the basis for germline antibody recognition of diverse antigens.
  • To computationally redesign antibodies for multi-antigen binding.

Main Methods:

  • Utilized the Rosetta multi-state design process for computational antibody redesign.
  • Focused on antibodies encoded by three VH gene segments.
  • Predicted antibody sequences for the entire heavy chain variable region, including framework and CDR mutations.

Main Results:

  • Predicted antibody sequences closely matched germline gene sequences, indicating residues critical for polyspecificity.
  • Computational design reversed antibody maturation in silico to achieve polyspecificity.
  • Designing for single-antigen binding yielded mature-like antibody sequences, mimicking natural maturation.
  • Identified key positions in VH gene (CDR1, CDR2, framework) crucial for germline antibody polyspecificity.

Conclusions:

  • The Rosetta algorithm accurately models antibody-antigen recognition.
  • Germline antibody sequences, particularly in framework regions and CDR1/CDR2, are key to polyspecificity.
  • Computational design can rationally engineer antibodies with retained polyspecificity for diverse epitope binding.