Resolving SARS-CoV-2 CD4 + T cell specificity via reverse epitope discovery.

Autor:	Pogorelyy MV; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38103, USA., Rosati E; Institute of Clinical Molecular Biology, Christian-Albrecht University of Kiel, Kiel, Germany; Institute of Immunology, Christian-Albrecht University of Kiel, Kiel, Germany., Minervina AA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38103, USA., Mettelman RC; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38103, USA., Scheffold A; Institute of Immunology, Christian-Albrecht University of Kiel, Kiel, Germany., Franke A; Institute of Clinical Molecular Biology, Christian-Albrecht University of Kiel, Kiel, Germany., Bacher P; Institute of Clinical Molecular Biology, Christian-Albrecht University of Kiel, Kiel, Germany; Institute of Immunology, Christian-Albrecht University of Kiel, Kiel, Germany. Electronic address: p.bacher@ikmb.uni-kiel.de., Thomas PG; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38103, USA. Electronic address: paul.thomas@stjude.org.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2022 Aug 16; Vol. 3 (8), pp. 100697. Date of Electronic Publication: 2022 Jul 01.
DOI:	10.1016/j.xcrm.2022.100697
Abstrakt:	The current strategy to detect immunodominant T cell responses focuses on the antigen, employing large peptide pools to screen for functional cell activation. However, these approaches are labor and sample intensive and scale poorly with increasing size of the pathogen peptidome. T cell receptors (TCRs) recognizing the same epitope frequently have highly similar sequences, and thus, the presence of large sequence similarity clusters in the TCR repertoire likely identify the most public and immunodominant responses. Here, we perform a meta-analysis of large, publicly available single-cell and bulk TCR datasets from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals to identify public CD4 + responses. We report more than 1,200 αβTCRs forming six prominent similarity clusters and validate histocompatibility leukocyte antigen (HLA) restriction and epitope specificity predictions for five clusters using transgenic T cell lines. Collectively, these data provide information on immunodominant CD4 + T cell responses to SARS-CoV-2 and demonstrate the utility of the reverse epitope discovery approach. Competing Interests: Declaration of interests P.B. and A.S. are consultants of Miltenyi Biotec, who own IP rights concerning parts of the ARTE technology. P.G.T. has consulted and/or received honoraria and travel support from Illumina, Johnson and Johnson, and 10X Genomics. P.G.T. serves on the Scientific Advisory Board of Immunoscape and Cytoagents. The authors have applied for patents covering some aspects of these studies. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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