The hexapod robot is an innovative and flexible tool that researchers can use to study immune cells, with the aim of developing immunotherapies for autoimmune, cancer, and infectious diseases. The robot has six arms that are filled with substances that the immune system could perceive as foreign, such as pieces of protein from a tumor, virus, or bacteria. Researchers can use the hexapods to analyze vast arrays of immune cells, identifying which ones bind to the target foreign molecules and how the hexapod’s movements affect that binding.

White blood cells, known as T cells, are responsible for recognizing foreign pathogens that have been processed by dendritic cells. Dendritic cells are immune cells with long branching arms that catch pathogens and display fragments of the pathogens’ molecules on their surface. A person’s body contains trillions of unique T cells, each with a distinctive T cell receptor that is specifically tuned to detect a pathogenic molecule (antigen) on a dendritic cell. Researchers often seek to understand which T cells can recognize a particular pathogen, with the goal of improving the immune system’s ability to fight it. However, searching through trillions of T cells for the precise match is akin to finding a needle in a haystack.

Previous T cell research platforms relied on isolated antigens that differed from living dendritic cells, and thus failed to replicate the importance of physical force in the interaction between dendritic cells and T cell receptors. To overcome these obstacles, scientists created a small robotic dendritic cell impersonator. The robot consists of six arms made of silicon dioxide, the main component of sand, to which antigens can be attached. Its central magnetic core rotates.

The hexapod’s efficiency was tested using known antigen-T cell receptor pairs. After applying antigen copies to each of the hexapod’s six legs, the researchers submerged it in various T cell combinations. The hexapods only bound to the correct cell, even when the matching T cell was present in small quantities among many other T cells.

Lingyuan Meng says, “We were incredibly happy with how well the system worked. The fact that it could pick out the right T cells with such a high accuracy exceeded our expectations.”

The research team demonstrated their ability to examine the immune response that arose due to the binding of T cells to the hexapod. They were able to identify which of the two T cells bound to the hexapod more strongly, leading to an increased immune activity. The team also discovered that the immune responses triggered by the force of the spinning hexapod were stronger than those caused by the binding of the same T cells to static antigens.

Huang says, “We’d now like to begin applying this to other antigens, including those from human cancers and pathogens. There are a lot of questions, both basic scientific questions and clinically relevant ones, that can be explored using these hexapods.”

The hexapods could be used to determine which antigens are most strongly responded to by T cells.

This news is a creative derivative product from articles published in famous peer-reviewed journals and Govt reports:

References:
1. Huang, X., et al. (2024) Multimodal probing of T cell recognition with hexapod heterostructures. Nature Methods. doi/10.1038/s41592-023-02165-7
2. Neal, L. R. et al. The basics of artificial antigen presenting cells in T cell-based cancer immunotherapies. J. Immunol. Res. Ther. 2, 68–79 (2017).
3. Karlsson, A. C., Humbert, M. & Buggert, M. The known unknowns of T cell immunity to COVID-19. Sci. Immunol. 5, eabe8063 (2020).
4. Rurik, J. G. et al. CAR T cells produced in vivo to treat cardiac injury. Science 375, 91–96 (2022).
5. Super, M. et al. Biomaterial vaccines capturing pathogen-associated molecular patterns protect against bacterial infections and septic shock. Nat. Biomed. Eng. 6, 8–18 (2022).

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