Antibody sequence determinants of viral antigen specificity

Area of Science:

• Immunology
• Molecular Biology
• Bioinformatics

Background:

• Antibodies are crucial for fighting viral infections, but the link between antibody sequence and antigen specificity is not fully understood.
• Existing methods often analyze antibody sequences and antigen specificities separately, limiting comprehensive insights.
• Understanding these determinants is vital for developing effective antibody therapeutics and vaccines.

Purpose of the Study:

• To map antibody sequences to antigen specificities using a large-scale dataset.
• To identify patterns in antibody variable gene usage, gene pairing, and somatic hypermutation related to viral antigens.
• To define criteria for public antibody clonality and predict antigen specificity.

Main Methods:

• Utilized LIBRA-seq technology to link antibody sequences with antigen specificities from thousands of B cells.
• Screened antibody repertoires from healthy individuals against 20 diverse viral antigens.
• Analyzed sequence data for variable gene usage, gene pairing, somatic hypermutation, and convergent antiviral signatures.

Main Results:

• Discovered virus-specific patterns in antibody gene usage and convergent antiviral signatures across individuals.
• Identified public antibody clonotypes, indicating shared recognition of viral antigens.
• Found that a CDRH3 amino acid identity threshold of 70% predicts shared antigen specificity for B cells with identical variable gene combinations.

Conclusions:

• Established a quantifiable link between antibody sequence and antigen specificity.
• Provided experimental evidence supporting a 70% CDRH3 identity threshold for defining public antibody clonality.
• This work offers a method to predict B-cell antigen specificity, aiding in the annotation of B-cell receptor data and informing vaccine and therapeutic development.