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Updated: Aug 29, 2025
Cell Surface Receptor Identification Using Genome-Scale CRISPR/Cas9 Genetic Screens
Published on: June 6, 2020
Ligand Identification for Orphan MHC-Agnostic T-Cell Receptors by Whole Genome CRISPR-Cas9 Screening
Michael D Crowther1,2, Mateusz Legut1,3, Andrew K Sewell4
1Division of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
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.
Insights
Killer T-cells are crucial for immunity, detecting threats inside cells. This study introduces a new unbiased method for discovering T-cell receptor ligands, expanding our understanding of immune responses beyond conventional pathways.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Killer T-cells are vital for immune responses against infections and cancer.
- They typically identify intracellular anomalies via peptides presented by Major Histocompatibility Complex (MHC) molecules.
- Emerging evidence suggests T-cells can detect intracellular changes through non-MHC pathways.
Purpose of the Study:
- To develop and present an unbiased methodology for discovering T-cell receptor (TCR) ligands.
- To enable the identification of novel TCR-antigen interactions independent of prior knowledge.
Main Methods:
- The study describes a novel, unbiased approach for T-cell receptor ligand discovery.
- This methodology does not require pre-existing information about the antigen's nature.
Main Results:
- The developed methodology allows for the identification of T-cell receptor ligands.
- It provides a new tool for exploring immune recognition pathways beyond conventional MHC-restricted antigen presentation.
Conclusions:
- The described unbiased methodology facilitates the discovery of T-cell receptor ligands.
- This approach broadens the scope of understanding T-cell recognition of pathogens and cancer cells, including non-MHC mediated responses.
