The tiny building block of one's life, the cell has a secret revealed in its exterior, designed with hundreds of thousands of molecular particles that aid immune cells in identifying a friend or a foe.
Those molecules are antigens that activate the immune system to initiate an attack. However, it is hard for experts to distinguish those antigens because of unique variations in every individual.
T Cell Can Recognize Disease-Indicating Peptides
A Stanford University team of scientists led by Polly Fordyce, a scholar at Sarafan CheM-H, has created a new approach to quickly and accurately identify which antigen can lead to a stronger immune response.
The team's study was published in Nature. According to the group, the research can aid scientists in inventing more compelling cancer immunotherapies.
"T Cells," a classification of the body's immune cells, creep along with other cells as they monitor the body.
In their study, the researchers used T cell receptors to read molecular peptides, or small amounts of proteins, which are cradled in a larger kind of protein called histocompatibility complexes (pMHCs) that project from cell exteriors.
Healthy host cells have pMHCs that do not trigger an immune response. However, when T cells recognize disease-indicating peptides, they are activated and find and kill cells with foreign signatures.
It remains a mystery how T cells distinguish antigenic peptides from host peptides to avoid the mistake of killing the host cells.
Collaborative Work of Scientists and Researchers
"A T cell can detect a single antigenic peptide amongst a sea of 10,000 or 100,000 non-antigenic peptides being displayed on cell surfaces," said Fordyce.
The factor for selectivity is within the T cell crawl. The sliding puts the T cells' stress on the bonds amongst the peptides and receptors, and most of the additional stress is sufficient to break that bond.
But at certain times, it has an opposing effect. Professor Chris Garcia, the co-author of the study and professor of cellular and molecular physiology and structural biology, had earlier shown that the numerous antigenic peptides with T cell receptor interaction had grown stronger in reaction to sliding.
Fordyce compared it to a Chinese finger trap, saying that when they pull a piece at the receptor-antigen interchange, the binding stays lengthy.
The Cellular Mockery
Specifying the finest antigen-receptor pairs needs continuous application in that sliding, or shearing, between the peptide and the T cell and gauging the activation of the T cell.
To get sufficient data for numerous possible T cell receptor pairs, the sliding' can be done a thousand times.
But the current methods are time-consuming and the result can be measurable by one peptide with thousands of T cells per day.
New method that will help target specific immune cells
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The study's first author, and postdoctoral scholar, Yinnian Feng, crafted a trick that permits the researchers to count 20 different peptides interacting with thousands of T cells in more than 4 hours.
Assembling a simplified system that mimics the cells with sagging peptides, the scientists created tiny spherical beads from a material that expands during heat contact. It is linked to a few molecules of a given peptide-studded pMHC to their exteriors.
After sedimenting a T cell atop each bead and staying long for the receptors to attach to the peptides, they slightly heated the gathered beads. Its expansion arises from the gap between rope points, and the related sliding of the T cell mimics the energy it experiences along the cells in the body.
Initial Scientific Results
These scientists could do hundreds of separate experiments resembling the 'beads system' with different colors, making it clearer to track numerous pMHCs. By conducting cross-referencing those visuals, it will tell them the antigens with the strongest T cell response.
The team's demonstration platform showed 21 distinctive peptides, and the results were confirmed.
The activating and non-activating peptides in one T cell receptor uncovered an unrecognized antigen that caused a strong T cell reaction.
In the Garcia lab, they have also begun to understand the challenges in immunotherapy.
The T cell receptors form the loftiest associational interaction with the labs' antigen. They are constantly activated by non-antigenic peptides in the body, which is a dangerous side effect that can destroy healthy cells.
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