In order to kill a pathogen invading the human body, T cells bind to it through T cell receptors TCR. This binding initiates the formation of a microcluster that includes hundreds of TCR molecules.
These microclusters are very important to initiate and sustain the immune signal.
TCR function by forming a complex (TCR/CD3) with CD3,CD45, on the other hand, is not part of the complex, but it regulates the formation of the clusters.
Single molecule imaging was used to trace the movement of CD3 and CD45 around the microclusters. The researchers discovered that the dynamics of the two molecules depended on their location relative to the microclusters and could be used to determine their interactions with the microclusters.
The kinetics showed CD3 and CD45 could take either a fast or slow mobility state. Inside the microcluster, the slow mobility state was dominant, reflecting stronger interactions between the two molecules and the microcluster. Outside and at the boundary, however, the fast mobility state was dominant. Yet a small fraction of molecules behaved according to the slow mobility state, suggesting that TCR nanoclusters exist at the outside or boundary of the microcluster.
The dynamics and kinetics at the single molecule level is very important for defining the molecular mechanisms of biological functions. Along with the new development of biopharmaceuticals related to immune control, elucidation of the mechanism of T cell activation is becoming more important in clinical application.
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