A recent study found that, T cells - the public security of immune system can use of a mechanical "handshake" to differentiate the cells they encounter are friend or foe. Research results published in the US National Academy of Sciences (PNAS) of May 2 was done by physical and chemist Khalid Salaita at Emory University who is specialized in cellular processes of mechanical force in collaboration with Brian Evavold at Emory University School of Medicine and Microbiology and Immunology.
Salaita said, "We provide the first direct evidence that, T cells to other cells to produce precision mechanical traction force. We show that this traction force to decide whether to launch a T cell immune response is extremely important. If one kind of traction force easily released, similar to casual handshake, then the other is a 'friend'. If it indicates a stronger pull the other side is the 'enemy' ".
T cells in the body constantly patrol, looking for foreign invaders. They are known to have a T-cell receptor molecule (TCR), recognize a specific antigen may be a peptide or pathogenic cell surface of cancer cells. When T cells detected an antigen-presenting cells (APC), which is connected to a TCR ligand APC or binding molecules. If the T cells is determined that the ligand is foreign, it will quickly be activated and begin injecting calcium. Calcium is to recruit other cells to come and give a portion of the signal chain to start the immune response.
For decades, scientists have known this process, but they did not fully understand "T cell antigen ligands how to distinguish a small modification, and how it responds to this decision." Salaita said: "If you do this kind of T-cell responses as a purely chemical process, and cannot fully explain the extraordinary specificity of binding when you select two components - TCR and the ligand on the cell surface, and. just let them combined in one solution, you cannot predict what will it causes a strong or a weak immune response."
The researchers speculated that mechanical forces may also play a role in T-cell responses, since T cells are locked even if combined with a ligand antigen, can continue to move. To test this idea, Salaita laboratory developed a tension sensor based on gold nanoparticle DNA can fluoresce in response to a skin Newton force is minimal mechanical force - about the weight of an apple million millionth.
Researchers using T cells from mice of the experimental design, allow them to test peptides comprising 8 amino acids (slight mutation) ligands. Salaita said, "We swap out fourth amino acid positions, to produce a very subtle chemical changes in the ligand, in the absence of a mechanical assembly, it is difficult to distinguish."
Salaita explains, "When a T cell across the cell surface, and encountered a ligand, it drag it. It will not be hard to drag; this is a very precise and minimal drag, not sustained .T cells and stop the drag, drag and stop across the entire surface. it's like the T cells are doing a mechanical test ligand."
During the experiment, when T cells encounter an anchor ligand with weak and not fully activated. In contrast, when T cells encounter having a solid anchor ligand, T cells become activated, thus indicating that it has undergone a skin Newton force resistance.
Researchers tension probe by using different stiffness detection of T cells to implement the pull size. 19 Newton force in response to skin probe does not fluoresce, but more flexible, the probe 12 Newton force the skin to produce high signal. After the probe fluoresces, T cells turn their calcium pump and an increase in intracellular calcium concentration, thereby indicating that T cells are launching an immune response.
Salaita said, "We were able to identify a series of chemical and mechanical cascade. First, T cells use a very special and fine mechanical drag force, to distinguish between friend and foe when it feels a precise skin Newton power level in response to such force when dragging, T cell realize it has encountered a foreign object, and send a signal to attack."
This finding may help us find therapies for autoimmune diseases and develop cancer immunotherapy. Salaita said, "There is another molecule cancer cells can make T cells remain 'drunk' or 'sleepy' state, so that they cannot function properly. Understanding of the mechanical forces for an effective immune response involved more can help us develop some way to evade the defenses of cancer cells."
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