Nature Methods: Find antigens that trigger specific immune cells faster and more accurately

The secret of a cell can be revealed from its surface, which is decorated with tens of thousands to hundreds of thousands of molecules, helping immune cells distinguish between enemies and enemies

A team of Stanford scientists led by Polly Fordyce has developed a new method that can predict more quickly and accurately which antigen will cause a strong immune response

T cells are immune cells that crawl and squeeze past other cells as they patrol the body, using T cell receptors to read peptides, or short fragments of proteins— proteins that are wrapped in larger proteins projected from the cell surface called master histocompatibility complexes (pmhc).

Fordyce, an assistant professor of bioengineering and genetics, said: "T cells can detect one antigenic peptide in 10,000 to 100,000 non-antigenic peptides

The key to selectivity lies in the crawling of T cells

"It's a bit like the Chinese finger cuffs (Chinese finger cuffs), a magic tool," Fordyce says, "and when you pull the receptor and antigen interaction a little bit, this binding actually lasts longer

Cell mimicry

Determining the optimal antigen receptor pair requires simultaneous application of sliding or shearing forces between peptides and T cells, and measuring T cell activation, ideally thousands of times, to obtain reproducible data

Yinnian Feng, a postdoc and the study's lead author, developed a technique that allowed the research team to measure the interaction of 20 unique peptides with thousands of T cells in less than 5 hours

To make a simplified system that mimics suspended peptide cells, they built small spherical beads out of a material that expands when heated and attaches several molecules of a given peptide granule pMHC to their surface

They can conduct hundreds of individual experiments in parallel by using each unique color-coded bead, which makes it possible

In their platform demonstration, the research team demonstrated 21 unique polypeptides, and their results confirmed a known activated and non-activated polypeptide for a T cell receptor and revealed a previously unknown antigen that can induce a strong T cell response

They hope that this fast and small-cell approach, or an optimized approach, could one day be used to improve personalized immunotherapy

"This platform could help improve T cell engineering specifically targeting cancer cells, as well as determining which antigens can effectively activate a patient's own T cells, thereby targeting cancer cells

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