A Framework to Identify Antigen-Expanded T Cell Receptor Clusters Within Complex Repertoires.

ABSTRACT: Common approaches for monitoring T cell responses are limited in their multiplexity and sensitivity. In contrast, deep sequencing of the T Cell Receptor (TCR) repertoire provides a global view that is limited only in terms of theoretical sensitivity due to the depth of available sampling; however, the assignment of antigen specificities within TCR repertoires has become a bottleneck. This study combines antigen-driven expansion, deep TCR sequencing, and a novel analysis framework to show that homologous 'Clusters of Expanded TCRs (CETs)' can be confidently identified without cell isolation, and assigned to antigen against a background of non-specific clones. We show that clonotypes within each CET respond to the same epitope, and that protein antigens stimulate multiple CETs reactive to co

SUBMITTER: Ceglia V 

PROVIDER: S-EPMC8670329 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature