Nature sub-journal: New breakthrough in cancer immunotherapy, Stanford University finds new way to trigger antigens of specific immune cells

Scientists develop new method to find antigens that trigger specific immune cells faster and more accurately

The secrets of a cell can be revealed from its surface

A team of scientists at Stanford University has developed a new method to more quickly and accurately predict which antigen will trigger a strong immune response

T cells are a type of immune cell that crawls and squeezes past other cells as they patrol the body

"T cells can detect an antigenic peptide among 10,000 to 100,000 non-antigenic peptides on the cell surface," said Fordyce, assistant professor of bioengineering and genetics

The key to selectivity lies in the crawling of T cells

Fordyce said

imitation of cells

Finding the optimal antigen-receptor pair requires simultaneously applying a sliding or shearing force between the peptide and T cells, and measuring T cell activation

Postdoctoral scholar Yinnian Feng, the study's first author, developed a trick that allowed the research team to measure the interaction of 20 unique peptides with thousands of T cells in less than five hours

To create a simplified system that mimics suspended polypeptide cells, they constructed small spherical beads of a material that expands when heated and attaches several molecules of a given polypeptide particle pMHCs to their surfaces

They could run hundreds of separate experiments in parallel by using each unique color-labeled bead, which made it possible to track multiple different pMHCs

In a demonstration of their platform, the research team showed 21 unique peptides, their results confirmed a T cell receptor known to activate and non-activating peptides, and revealed a previously unknown antigen that can induce strong T cellular response

Using their technique, the research team characterized T-cell receptors that can specifically recognize tumor antigens without generating off-target responses

Scientists hope that this method, which is fast and requires very few cells, or an optimized method, could one day be used to improve personalized immunotherapy

Reference: Bead-based method for high-throughput mapping of the sequence- and force-dependence of T cell activation