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

Autor:	Kovaleva VA; Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Pattinson DJ; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA., Barton C; Birkbeck, University of London, WC1E 7HX London, UK., Chapin SR; Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA., Minervina AA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Richards KA; David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Sant AJ; David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA., Thomas PG; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Pogorelyy MV; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Meyer HV; Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 08. Date of Electronic Publication: 2024 Feb 08.
DOI:	10.1101/2023.11.28.569052
Abstrakt:	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. Competing Interests: Competing interests PGT has consulted for Pfizer, JNJ, Cytoagents, 10X, and Illumina, and serves on the SAB for Shennon Bio and Immunoscape. PGT, AAM, and MVP have patents related to TCR amplification, cloning, and applications thereof. The authors declare no other competing interests.
Databáze:	MEDLINE
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