T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes
Tomasz Kula, Mohammad H Dezfulian, Charlotte I Wang, Nouran S Abdelfattah, Zachary C Hartman, Kai W Wucherpfennig, Herbert Kim Lyerly, Stephen J Elledge, Tomasz Kula, Mohammad H Dezfulian, Charlotte I Wang, Nouran S Abdelfattah, Zachary C Hartman, Kai W Wucherpfennig, Herbert Kim Lyerly, Stephen J Elledge
Abstract
T cell recognition of specific antigens mediates protection from pathogens and controls neoplasias, but can also cause autoimmunity. Our knowledge of T cell antigens and their implications for human health is limited by the technical limitations of T cell profiling technologies. Here, we present T-Scan, a high-throughput platform for identification of antigens productively recognized by T cells. T-Scan uses lentiviral delivery of antigen libraries into cells for endogenous processing and presentation on major histocompatibility complex (MHC) molecules. Target cells functionally recognized by T cells are isolated using a reporter for granzyme B activity, and the antigens mediating recognition are identified by next-generation sequencing. We show T-Scan correctly identifies cognate antigens of T cell receptors (TCRs) from viral and human genome-wide libraries. We apply T-Scan to discover new viral antigens, perform high-resolution mapping of TCR specificity, and characterize the reactivity of a tumor-derived TCR. T-Scan is a powerful approach for studying T cell responses.
Keywords: T cell epitope; T cell screening; TCR epitope; TCR-specificity; antigen discovery; epitope discovery; epitope mutagenesis; epitope screening; immunological screening; off-target screening; peptide MHC recognition.
Conflict of interest statement
DECLARATION OF INTERESTS
T.K., M.H.D. and S.J.E. are inventors of and have submitted a patent on the T-Scan technology. T.K. and S.J.E. are also founders of, and hold equity in, TScan Therapeutics, Inc., a company that has licensed this technology. The interests of S.J.E. were reviewed and are managed by BWH and Partners HealthCare in accordance with their conflict of interest policies.
Copyright © 2019 Elsevier Inc. All rights reserved.
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Source: PubMed