For CD4+T cells, TCR T and CD4 are very important receptor molecules. In the activation process, TCR and CD4 are combined with the MHC- antigen complex to achieve signal transmission. Those facts have been confirmed by many studies, and how these molecules are arranged on the cell membrane has not have a consistent conclusion.
Now, I will introduce how researchers explored the TCR, CD4 and other molecules on the surface of CD4+ cell by using super resolution microscopy.
First, they used PALM (photoactivated localization microscopy) to observe the distribution of CD4 on the surface of activated T cells. The results showed that CD4 was not randomly distributed on the cell membrane even in the absence of activation. They would spontaneously gather to form nanoscale clusters that were significantly increased in cell activation.
After that, they were using the red fluorescent protein and green fluorescent protein to label CD3 chain and CD4, comparing the distribution characteristics of CD4 and TCR before and after stimulation. The results showed that before activating, 13-18 CD3 chain (TCR) formed the "island" structure, while 4-8 CD4 molecules formed a "island" structure. The contact between CD4 and CD3 chain only occurred in the edge region of each "island" structure. In the active state, the two types of "island" had been isolated from each other greatly. The above results indicated that the contact between TCR and CD4 only occurred in the edge zone of their respective clusters (about 50%), regardless of the active state.
In addition, they used another set of super resolution microscopy technology—"dSTORM" (direct stochastic optical reconstruction microscopy) to repeat the above experiments. Results were consistent with those of the PALM. After that, they used the technique to compare the distribution of TCR before and after the stimulation. The results showed that in the stimulus state, TCR would be clustered together to form a large mass structure (supramolecluar activation clusters, SMAC), and CD4 molecules would be "excluded" from the SMAC structure.
This is the distribution of the T cell receptor group. I believe it is very helpful for us to understand the formation of the T cell receptor complex.
About the author:
Creative Biolabs CellRapeutics is a leading expert on the immunotherapy of TCR and CAR NK cells. In the entire process of drug development, we can provide one-stop customized services, including TCR and CAR T structure products.