Difference between revisions of "Part:BBa K321004"
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In wild-type NK cells, Killer cell immunoglobulin-like receptors (KIRs) with  long cytoplasmic domains inhibit cell mediated cytotoxicity upon ligand binding. They possess a immune tyrosine-based inhibitory motif (ITIM) that when phosphorylated recruits phosphotases like SHP-1 that decrease the activation molecules involved in cell signaling.  
 
In wild-type NK cells, Killer cell immunoglobulin-like receptors (KIRs) with  long cytoplasmic domains inhibit cell mediated cytotoxicity upon ligand binding. They possess a immune tyrosine-based inhibitory motif (ITIM) that when phosphorylated recruits phosphotases like SHP-1 that decrease the activation molecules involved in cell signaling.  
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ANDN gate
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In order to understand the ANDN gate, let us set up a hypothetical situation in which antigen A and antigen B are expressed on the membrane surface of healthy cells. Since cancer cells typically discard many surface proteins as a result of genetic mutation, we represent this discarded protein as antigen B in our scenario. Our ANDN gate is designed to address this issue by triggering cytotoxicity in the presence of antigen A and absence of antigen B. Therefore, cancerous cells that express antigen A and “hide” antigen B will be targeted. Healthy cells expressing both antigen A and B will not set off the activation of the ANDN gate. This concept is valuable for ensuring a level of specificity that prevents the overly indiscriminate activation of killer cells.
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We tested two different ANDN gate designs to determine their effects on target recognition. To achieve the level of specificity as described by our hypothetical situation, we have set two different antigen binding domains to recognize antigen A and antigen B, respectively. Attached to the domain that recognized antigen A was an ITAM-bearing intracellular chain, from either the CD3 zeta or Fc receptor gamma, that signaled for killer cell activation. The domain that recognized antigen B, the antigen found in healthy cells, was fused to the intracellular portion of the ITIM-based receptor KIR3DL1, which inhibits killer cell activation. As a result of this combination, target cells expressing only antigen A would trigger killer cell activation, and target cells that do not express antigen A would not. Target cells that express both antigens A and B would be unharmed due to ITIM inhibitory signals, meaning that the presence of antigen B overwrites the input of antigen A. In conclusion, only a specific combination of surface antigens can set off the chain of activation, resulting in increased precision of detection and cancer killing.
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Revision as of 02:30, 28 October 2010

intracellular chain of KIR3DL1

Encodes the intracellular signaling chain of the KIR3DL1 immune receptor. Inhibits immune cell activation via the ITIM (immunoreceptor tyrosine-based inhibition motif) motif.


Usage and Biology

In wild-type NK cells, Killer cell immunoglobulin-like receptors (KIRs) with long cytoplasmic domains inhibit cell mediated cytotoxicity upon ligand binding. They possess a immune tyrosine-based inhibitory motif (ITIM) that when phosphorylated recruits phosphotases like SHP-1 that decrease the activation molecules involved in cell signaling. 

ANDN gate

In order to understand the ANDN gate, let us set up a hypothetical situation in which antigen A and antigen B are expressed on the membrane surface of healthy cells. Since cancer cells typically discard many surface proteins as a result of genetic mutation, we represent this discarded protein as antigen B in our scenario. Our ANDN gate is designed to address this issue by triggering cytotoxicity in the presence of antigen A and absence of antigen B. Therefore, cancerous cells that express antigen A and “hide” antigen B will be targeted. Healthy cells expressing both antigen A and B will not set off the activation of the ANDN gate. This concept is valuable for ensuring a level of specificity that prevents the overly indiscriminate activation of killer cells.

We tested two different ANDN gate designs to determine their effects on target recognition. To achieve the level of specificity as described by our hypothetical situation, we have set two different antigen binding domains to recognize antigen A and antigen B, respectively. Attached to the domain that recognized antigen A was an ITAM-bearing intracellular chain, from either the CD3 zeta or Fc receptor gamma, that signaled for killer cell activation. The domain that recognized antigen B, the antigen found in healthy cells, was fused to the intracellular portion of the ITIM-based receptor KIR3DL1, which inhibits killer cell activation. As a result of this combination, target cells expressing only antigen A would trigger killer cell activation, and target cells that do not express antigen A would not. Target cells that express both antigens A and B would be unharmed due to ITIM inhibitory signals, meaning that the presence of antigen B overwrites the input of antigen A. In conclusion, only a specific combination of surface antigens can set off the chain of activation, resulting in increased precision of detection and cancer killing.


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
    COMPATIBLE WITH RFC[1000]