copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling.

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:	Meyer, Hannah V. Chapin, Sarah Kovaleva, Vasilisa
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:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41330

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