Part:BBa_K321003

intracellular chain of CD3 zeta

Encodes the intracellular signaling domain of the CD3 zeta molecule of the T-Cell Receptor complex. The sequence encodes the three ITAMs (Immunoreceptor tyrosine-based activation motif) that can activate immune cells.

Usage and Biology

The CD3 zeta molecule activates immune T cells upon ligand binding to the T-Cell Receptor complex. The immunoreceptor tyrosine-based activation (ITAM) motifs in the intracellular domain of CD3 zeta recruits kinases that activate downstream molecules involved in cell signaling. This intracellular domain has been shown to function in a modular manner. It can be fused to different extracellular ligand binding domains to create functional synthetic receptors.

Function

This part was shown to activate killer cells by the UCSF 2010 team. We successfully used this part in our proof of concept logic gate design for greater precision of killing towards cancer cells. The figure below shows that the part performs its activating function as expected. On the X-axis are different types of target cells, which represent normal and cancer cells expressing different combinations of surface antigents in our experiment. The Y-axis shows the activation levels of killer cells engineered to express synthetic receptors, one of which bears this part as its intracellular domain. In the presence of antigen A that activates the synthetic receptor bearing this part (left chart, solid green bar), we detected increased killer cell activation as compared with the control (gray bar). Binding of antigen B to the other synthetic receptor over-writes the activation signal triggered by antigen A and inhibits killer cell activation in our experimental design. This is why target cells expressing both antigens A and B did not increase killer cell activation. For more information please see our wiki.

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  INCOMPATIBLE WITH RFC[1000]

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