T cell antigen discovery via trogocytosis

Area of Science:

• Immunology
• Molecular Biology
• Cancer Research

Background:

• T cell receptor (TCR) ligand discovery is crucial for understanding anti-tumor immunity.
• Identifying TCR ligands aids in developing novel cancer immunotherapies.

Purpose of the Study:

• To develop a novel cell-based platform for T cell receptor (TCR) ligand discovery.
• To leverage trogocytosis for efficient identification of cognate TCR ligands.

Main Methods:

• Developed a platform utilizing trogocytosis, a membrane transfer phenomenon.
• Co-incubated T cells with orphan TCRs and target cells presenting peptide-MHC libraries.
• Isolated specifically labeled target cells for ligand sequencing.

Main Results:

• Demonstrated specific membrane protein transfer from T cells to target cells presenting cognate peptide-MHCs.
• Successfully validated the method using clinically relevant TCRs.
• Identified a cognate neoepitope for a subject-derived neoantigen-specific TCR.

Conclusions:

• Target cell trogocytosis is a robust and effective tool for TCR ligand discovery.
• This platform facilitates the study of tumor immunology and immunotherapy target identification.