Repertoire-scale measures of antigen binding

Area of Science:

• Immunology
• Computational Biology
• Bioinformatics

Background:

• Adaptive immunity relies on antibodies and T cell receptors (TCRs) for epitope binding.
• Current repertoire analysis methods often focus on sequence diversity, potentially missing functional insights.
• Understanding repertoire function is crucial for diagnosing immune status and responses.

Purpose of the Study:

• To develop a framework for describing immune repertoires based on epitope-binding properties.
• To analyze the structure of antibody and TCR repertoires.
• To demonstrate the framework's utility in distinguishing immune responses and identifying immune profiles.

Main Methods:

• Analysis of thousands of antibody-antigen and TCR-peptide-major-histocompatibility-complex binding interactions.
• High-throughput repertoire data analysis from over 400 samples.
• Development of a novel framework categorizing repertoires by binding properties.

Main Results:

• Identified repertoires as composed of overlapping classes of antibodies and TCRs with similar binding characteristics.
• Demonstrated the framework's ability to differentiate specific immune responses from bystander activation in vaccinees.
• Showcased potential for stratifying cytomegalovirus (CMV)-infected individuals and identifying immunological 'super-agers'.

Conclusions:

• Immune repertoires can be effectively characterized by the binding properties of their constituent antibodies and TCRs.
• The proposed framework offers a functional dimension to repertoire assessment, enhancing understanding of immune status.
• This approach has significant implications for personalized medicine and immunological research.