T cell responses against SARS-CoV-2 may provide durable protection against infections, and T cells targeting the virus may be useful for COVID-19 treatments.
To best utilize T cells for prevention and treatment, it is critical to understand the viral targets, or peptides, that T cells recognize. To date, researchers have relied on in silico methods to predict immunogenic viral peptides, but little has been done to experimentally validate predicted targets.
Researchers led by Ke Pan, Ph.D., Yulun Chiu, Ph.D., and eCassian Yee, M.D., used mass spectrometry to sequence viral peptides from the surface of infected cells and verify which could elicit T cell responses. They demonstrated that many predicted peptides are not immunogenic and should not be pursued further. The team also identified new immunogenic peptides from highly conserved viral proteins, which do not mutate frequently, offering ideal targets for therapeutic approaches.
The researchers sequenced the T cell receptor (TCR) for one of these targets, allowing them to engineer the first reported TCR T cell capable of recognizing and targeting infected cells.