T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes.
Antigen Presentation
/ immunology
Antigens, Neoplasm
/ genetics
Blood Donors
CD8-Positive T-Lymphocytes
/ metabolism
Epitopes, T-Lymphocyte
/ immunology
Female
Gene Knockout Techniques
Genes, MHC Class I
/ genetics
Granzymes
/ metabolism
HEK293 Cells
HLA Antigens
/ genetics
Humans
Neoplasm Proteins
/ genetics
Receptors, Antigen, T-Cell
/ immunology
Transduction, Genetic
Transfection
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
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
08 08 2019
08 08 2019
Historique:
received:
16
12
2018
revised:
20
04
2019
accepted:
09
07
2019
entrez:
10
8
2019
pubmed:
10
8
2019
medline:
10
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31398327
pii: S0092-8674(19)30774-3
doi: 10.1016/j.cell.2019.07.009
pmc: PMC6939866
mid: NIHMS1060689
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
Epitopes, T-Lymphocyte
0
HLA Antigens
0
MAGEA3 protein, human
0
Neoplasm Proteins
0
Receptors, Antigen, T-Cell
0
GZMB protein, human
EC 3.4.21.-
Granzymes
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1016-1028.e13Subventions
Organisme : NCI NIH HHS
ID : R01 CA173750
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI118633
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009216
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014236
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007598
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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