A team of Stanford scientists led by Dr. Polly Fordyce, an Institute Scholar at Sarafan ChEM-H, has developed a new method to quickly and more accurately predict which antigens will lead to a strong immune response. The research published in the journal Nature Methods can help scientists develop more effective cancer immunotherapies. The cell surface is covered with billions of molecules that can assist immune cells in distinguishing between friend and foe. Some of those projecting molecules are antigens that cause the immune system to attack, but identifying those antigens in the molecular forest can be challenging because they differ between individuals. During an immune response, T cells, a class of immune cells, crawl along and squish past other cells as they patrol the body, using T cell receptors to molecularly read signals that are projected on the cell surfaces. Healthy host cells display an array of major histocompatibility complexes (pMHCs) that do not trigger an immune response, but once T cells recognize disease-indicating peptides that bear a foreign signature, they become activated to find and kill such cells.

Hence, in the research, the study′s first author, postdoctoral scholar Yinnian Feng, developed a trick that allowed the team to measure 20 unique peptides interacting with thousands of T cells in less than five hours. He constructed small spherical beads from a material that expanded on heating and attached a few molecules of a given peptide-studded pMHC to their surfaces. After attaching a T cell atop each bead and waiting long enough for receptors to bind to the peptides, the beads were slightly heated. The bead′s expansion increases the distance between tether points, thereby mimicking the stretching of the T cell that it would experience while sliding along cells in the body. 

Using this trick, the team reaffirmed the mechanism of known activating and non-activating peptides for one T cell receptor. They have also begun to address a challenge in immunotherapy, i.e., the T cell receptors that form the highest affinity interactions with antigens in the lab are often 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 working with Dr. Chris Gracia, co-author of the study and professor of molecular and cellular physiology and structural biology, has characterized T cell receptors engineered to specifically recognize tumor antigens without off-target reactivity. 

(Source: https://www.business-standard.com/article/international/researchers-develop-new-approach-to-find-immune-cell-triggering-antigens-122090600060_1.html )