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Repertoire-scale measures of antigen binding

Antibodies and T cell receptors (TCRs) are the fundamental building blocks of adaptive immunity. Repertoire-scale functionality derives from their epitope-binding properties, just as macroscopic properties like temperature derive from microscopic molecular properties. However, most approaches to rep...

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Detalles Bibliográficos
Autores principales: Arora, Rohit, Arnaout, Ramy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407674/
https://www.ncbi.nlm.nih.gov/pubmed/35969768
http://dx.doi.org/10.1073/pnas.2203505119
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author Arora, Rohit
Arnaout, Ramy
author_facet Arora, Rohit
Arnaout, Ramy
author_sort Arora, Rohit
collection PubMed
description Antibodies and T cell receptors (TCRs) are the fundamental building blocks of adaptive immunity. Repertoire-scale functionality derives from their epitope-binding properties, just as macroscopic properties like temperature derive from microscopic molecular properties. However, most approaches to repertoire-scale measurement, including sequence diversity and entropy, are not based on antibody or TCR function in this way. Thus, they potentially overlook key features of immunological function. Here we present a framework that describes repertoires in terms of the epitope-binding properties of their constituent antibodies and TCRs, based on analysis of thousands of antibody–antigen and TCR–peptide–major-histocompatibility-complex binding interactions and over 400 high-throughput repertoires. We show that repertoires consist of loose overlapping classes of antibodies and TCRs with similar binding properties. We demonstrate the potential of this framework to distinguish specific responses vs. bystander activation in influenza vaccinees, stratify cytomegalovirus (CMV)-infected cohorts, and identify potential immunological “super-agers.” Classes add a valuable dimension to the assessment of immune function.
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spelling pubmed-94076742022-08-26 Repertoire-scale measures of antigen binding Arora, Rohit Arnaout, Ramy Proc Natl Acad Sci U S A Biological Sciences Antibodies and T cell receptors (TCRs) are the fundamental building blocks of adaptive immunity. Repertoire-scale functionality derives from their epitope-binding properties, just as macroscopic properties like temperature derive from microscopic molecular properties. However, most approaches to repertoire-scale measurement, including sequence diversity and entropy, are not based on antibody or TCR function in this way. Thus, they potentially overlook key features of immunological function. Here we present a framework that describes repertoires in terms of the epitope-binding properties of their constituent antibodies and TCRs, based on analysis of thousands of antibody–antigen and TCR–peptide–major-histocompatibility-complex binding interactions and over 400 high-throughput repertoires. We show that repertoires consist of loose overlapping classes of antibodies and TCRs with similar binding properties. We demonstrate the potential of this framework to distinguish specific responses vs. bystander activation in influenza vaccinees, stratify cytomegalovirus (CMV)-infected cohorts, and identify potential immunological “super-agers.” Classes add a valuable dimension to the assessment of immune function. National Academy of Sciences 2022-08-15 2022-08-23 /pmc/articles/PMC9407674/ /pubmed/35969768 http://dx.doi.org/10.1073/pnas.2203505119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Arora, Rohit
Arnaout, Ramy
Repertoire-scale measures of antigen binding
title Repertoire-scale measures of antigen binding
title_full Repertoire-scale measures of antigen binding
title_fullStr Repertoire-scale measures of antigen binding
title_full_unstemmed Repertoire-scale measures of antigen binding
title_short Repertoire-scale measures of antigen binding
title_sort repertoire-scale measures of antigen binding
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407674/
https://www.ncbi.nlm.nih.gov/pubmed/35969768
http://dx.doi.org/10.1073/pnas.2203505119
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