Novel methods to faster and more accurately find antigens triggering specific immune cells

A cell's secrets can be divulged by its surface, decorated with tens to hundreds of thousands of molecules that help immune cells determine friend from foe. Some of those protruding molecules are antigens that trigger the immune system to attack, but it can be difficult for scientists to identify those antigens, which often vary across individuals, in the molecular forest.

A team of Stanford scientists led by Polly Fordyce, has developed a new method to faster and more accurately predict which antigens will lead to a strong immune response. Their approach, which was reported in Nature Methods could help scientists develop more effective cancer immunotherapies.

The team showed, with 21 unique peptides, that their results confirmed known activating and non-activating peptides for one T cell receptor and uncovered a previously unknown antigen that induced a strong T cell response. Working with the Garcia lab, they have also already begun to address a challenge in immunotherapy: the T cell receptors that form the highest affinity interactions with antigens in the lab are often also activated by non-antigenic peptides in the body, a dangerous side effect that leads to the killing of healthy cells. Using their technology, the team characterized T cell receptors engineered to specifically recognize tumor antigens without off-target reactivity.

Ref:

Polly Fordyce, et al,bead-based method for high-throughput mapping of the sequence- and force-dependence of T cell activation, Nature Methods,DOI: 10.1038/s41592-022-01592-2