Kovaleva, Vasilisa A, Pattinson, David J, Barton, Carl, Chapin, Sarah R, Minervina, Anastasia A, Richards, Katherine A, Sant, Andrea J, Thomas, Paul G, Pogorelyy, Mikhail V, Meyer, Hannah V (November 2023) copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling. bioRxiv. (Submitted)
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Abstract
T cell receptor (TCR) repertoire diversity enables the orchestration of antigen-specific immune responses against the vast space of possible pathogens. Identifying TCR/antigen binding pairs from the large TCR repertoire and antigen space is crucial for biomedical research. Here, we introduce copepodTCR, an open-access tool for the design and interpretation of high-throughput experimental assays to determine TCR specificity. copepodTCR implements a combinatorial peptide pooling scheme for efficient experimental testing of T cell responses against large overlapping peptide libraries, useful for “deorphaning” TCRs of unknown specificity. The scheme detects experimental errors and, coupled with a hierarchical Bayesian model for unbiased results interpretation, identifies the response-eliciting peptide for a TCR of interest out of hundreds of peptides tested using a simple experimental set-up. We experimentally validated our approach on a library of 253 overlapping peptides covering the SARS-CoV-2 spike protein. We provide experimental guides for efficient design of larger screens covering thousands of peptides which will be crucial for the identification of antigen-specific T cells and their targets from limited clinical material.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions |
| CSHL Authors: | |
| Communities: | CSHL labs > Meyer Lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 29 November 2023 |
| Date Deposited: | 20 Dec 2023 18:29 |
| Last Modified: | 20 Dec 2023 18:32 |
| PMCID: | PMC10705480 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41330 |
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