학술논문

Defining T cell receptor repertoires using nanovial-based affinity and functional screening
Document Type
article
Source
bioRxiv. 4(01-27)
Subject
Biochemistry and Cell Biology
Biomedical and Clinical Sciences
Biological Sciences
Immunology
Vaccine Related
Infectious Diseases
Bioengineering
Biotechnology
1.1 Normal biological development and functioning
2.1 Biological and endogenous factors
Aetiology
Underpinning research
Inflammatory and immune system
Language
Abstract
The ability to selectively bind to antigenic peptides and secrete cytokines can define populations of cells with therapeutic potential in emerging T cell receptor (TCR) immunotherapies. We leverage cavity-containing hydrogel microparticles, called nanovials, each coated with millions of peptide-major histocompatibility complex (pMHC) monomers to isolate antigen-reactive T cells. T cells are captured and activated by pMHCs and secrete cytokines on nanovials, allowing sorting based on both affinity and function. The TCRs of sorted cells on nanovials are sequenced, recovering paired αβ-chains using microfluidic emulsion-based single-cell sequencing. By labeling nanovials having different pMHCs with unique oligonucleotide-barcodes we could link TCR sequence to targets with 100% accuracy. We identified with high specificity an expanded repertoire of functional TCRs targeting viral antigens compared to standard techniques.