To eliminate threats without damaging our normal cells and tissues, the immune system must be able to sensitively and specifically discriminate between the two. To accomplish this, T cell receptors (TCRs) on T cells recognize short protein fragments that are displayed on other cells via the MHC system. Upon recognition of an MHC-bound antigen, T cells are activated and proceed to eliminate those target cells. To date, however, there is no way to accurately predict which MHC-antigen complexes will drive efficient T cell activation, largely because standard screening assays do not accurately mimic physiologic T cell triggering.
Previously, Dr. Yinnian Feng demonstrated that shear forces applied to the MHC-antigen-TCR interaction play a crucial role in T cell recognition. Now, Feng aims to develop a screening assay that incorporates this insight through the use of ‘smart beads’ that apply well-calibrated and physiologic forces to T cells interacting with many different MHC-antigen sequences in parallel. This platform could potentially overcome current challenges in screening and revolutionize our ability to tailor treatments to particular patients by facilitating high-throughput and low-cost profiling of T cell activation profiles directly from patient samples.
Projects and Grants
High-throughput mapping of the sequence- and force-dependent landscape of T cell activation
Stanford University | All Cancers | 2020 | Polly M. Fordyce, Ph.D.
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