T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kula, T; Dezfulian, MH; Wang, CI; Abdelfattah, NS; Hartman, ZC; Wucherpfennig, KW; Lyerly, HK; Elledge, SJ

Published Date

  • August 8, 2019

Published In

Volume / Issue

  • 178 / 4

Start / End Page

  • 1016 - 1028.e13

PubMed ID

  • 31398327

Pubmed Central ID

  • 31398327

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2019.07.009

Language

  • eng

Conference Location

  • United States