Ligand Identification for Orphan MHC-Agnostic T-Cell Receptors by Whole Genome CRISPR–Cas9 Screening

Michael D. Crowther, Mateusz Legut, Andrew K. Sewell*

*Corresponding author for this work

Abstract

Killer T-cells play important roles in immunity to infection and cancer by detecting intracellular anomalies at the cell surface and destroying the cells that bear them. Conventional killer T-cells scan the intracellular proteome by sampling peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. It is becoming apparent that some T-cells can also respond to pathogens and neoplasms by sensing intracellular changes through molecules other than MHC. We describe an unbiased methodology for T-cell receptor ligand discovery that requires no a priori knowledge regarding the nature of the antigen.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
Number of pages12
Volume2574
Publication date2022
Pages3-14
DOIs
Publication statusPublished - 2022
SeriesMethods in Molecular Biology
ISSN1064-3745

Keywords

  • CRISPR
  • Lentivirus
  • Ligand discovery
  • MHC-independent
  • MR1
  • T-cell
  • Major Histocompatibility Complex
  • Receptors, Antigen, T-Cell/genetics
  • CRISPR-Cas Systems
  • Histocompatibility Antigens
  • Ligands

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