There is a new method for discovering T cell epitopes, recently detailed in a Cell article, T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes. T cell profiling technologies have long been a limitation to our understanding of T cell antigens, something that the creators of T-Scan hope to address.
How T-Scan Works
The researchers in this publication first constructed Epitope Discovery Cells (EDC) as target cells that were engineered to express only one HLA allele and to activate a recombinase enzyme that would only activate upon exposure to granzyme. This granzyme activation would only occur if the target cell was exposed to T cells that recognize the antigen presented on the selected HLA allele.
These activated EDC were then transfected with entire libraries of genes to discover if any antigens were present and targeted by T cells. The authors of the publication present data showing the use of this T-Scan technique to find T cell epitopes, both known and novel.
The Importance of T-Scan
This method could be a great leap forward in discovering T cell epitopes, particularly in the case where tumors from different individuals express different neo-antigens and neo-epitopes. T-Scan is a novel method that does not require the culture of T cells and allows for precise mapping of T cells to the peptides they recognize.
If relevant targets can be rapidly discovered, researchers will benefit from the opportunity to hone in on effective T cell-based therapies. Since different HLA alleles can be chosen for expression, T-Scan should also allow for discovery of dominant epitopes, even for rare HLA alleles.
The initial promise of T-Scan does not eliminate other methods of epitope discovery, but future comparison studies should further demonstrate the utility.