Probing TCR Specificity Using Artificial In Vivo Diversification of CDR3 Regions.

ABSTRACT: The T-cell receptor sequences expressed on cells recognizing a specific peptide in the context of a given MHC molecule can be explored for common features that might explain their antigen specificity. However, despite the development of numerous experimental and bioinformatic strategies, the specificity problem remains unresolved. To address the need for additional experimental paradigms, we report here on an in vivo experimental strategy designed to artificially diversify a transgenic TCR by CRISPR/Cas9-mediated mutagenesis of Tcra and Tcrb chain genes. In this system, an initially monoclonal repertoire of known specificity is converted into an oligoclonal pool of TCRs of altered antigen reactivity. Tracking the fate of individual clonotypes during the intrathymic differentiation process

SUBMITTER: Giorgetti OB 

PROVIDER: S-EPMC11739678 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature