Difference between revisions of "Part:BBa K4040002"

 
Line 3: Line 3:
 
<partinfo>BBa_K4040002 short</partinfo>
 
<partinfo>BBa_K4040002 short</partinfo>
  
−
Structure and function of the CAR&#947;:
+
<h3><b>Structure and function of the CAR&#947;</b></h3>
 
Researchers have identified that the common &#947; subunit of Fc receptors (FcR&#947;) have the potential ability to enhance the phagocytosis efficiency of the macrophages. We consequently constructed a chimeric antigen receptor containing the critical function domain of the FcR&#947;, expecting the permitting function of the FcR&#947;. There are three parts in our CAR, an &#945;S-scFv extracellular domain targeting the spike(S) protein of the SARS-CoV-2, a CD8 hinge and a CD8 transmembrane domain presented in the &#945;CD19 CAR for T cells permitting the signal transduction, a intracellular domain with the same structure of the FcR&#947; for the enhancement of the phagocytosis efficiency.
 
Researchers have identified that the common &#947; subunit of Fc receptors (FcR&#947;) have the potential ability to enhance the phagocytosis efficiency of the macrophages. We consequently constructed a chimeric antigen receptor containing the critical function domain of the FcR&#947;, expecting the permitting function of the FcR&#947;. There are three parts in our CAR, an &#945;S-scFv extracellular domain targeting the spike(S) protein of the SARS-CoV-2, a CD8 hinge and a CD8 transmembrane domain presented in the &#945;CD19 CAR for T cells permitting the signal transduction, a intracellular domain with the same structure of the FcR&#947; for the enhancement of the phagocytosis efficiency.
−
The mechanism of the CAR&#947;:
+
[[File:T--SMMU-China--synnotch 1.png|800px|thumb|center|]]
 +
<h3><b>The mechanism of the CAR&#947;</b></h3>
 
The function domain of the CAR&#947; mainly lies in the intracellular domain, namely the cytosolic Immunoreceptor Tyrosine-based Activation Motifs (ITAMs). The cytosolic Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) in the intracellular domain of the CAR&#947; will be phosphorylated by Src family kinases when the CAR&#947; is stimulated by its ligands S protein. The expression of S protein on the surface of SARS-CoV-2 is actually a strong stimulus of CAR&#947;-macrophages. The activated Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) will expose the SH2 binding domains for the SH2 matching domain. And the SH2 matching domain contains the kinase ZAP70 and the Syk in the T cells and the macrophages respectively. Protein Syk, a phagocytic signaling effector can then active the downstream signaling transduction cascades and initiate the phagocytosis in our CAR&#947;-macrophages eventually.
 
The function domain of the CAR&#947; mainly lies in the intracellular domain, namely the cytosolic Immunoreceptor Tyrosine-based Activation Motifs (ITAMs). The cytosolic Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) in the intracellular domain of the CAR&#947; will be phosphorylated by Src family kinases when the CAR&#947; is stimulated by its ligands S protein. The expression of S protein on the surface of SARS-CoV-2 is actually a strong stimulus of CAR&#947;-macrophages. The activated Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) will expose the SH2 binding domains for the SH2 matching domain. And the SH2 matching domain contains the kinase ZAP70 and the Syk in the T cells and the macrophages respectively. Protein Syk, a phagocytic signaling effector can then active the downstream signaling transduction cascades and initiate the phagocytosis in our CAR&#947;-macrophages eventually.
  

Revision as of 03:26, 3 September 2021


FcRγ Function Unit

Structure and function of the CARγ

Researchers have identified that the common γ subunit of Fc receptors (FcRγ) have the potential ability to enhance the phagocytosis efficiency of the macrophages. We consequently constructed a chimeric antigen receptor containing the critical function domain of the FcRγ, expecting the permitting function of the FcRγ. There are three parts in our CAR, an αS-scFv extracellular domain targeting the spike(S) protein of the SARS-CoV-2, a CD8 hinge and a CD8 transmembrane domain presented in the αCD19 CAR for T cells permitting the signal transduction, a intracellular domain with the same structure of the FcRγ for the enhancement of the phagocytosis efficiency.

T--SMMU-China--synnotch 1.png

The mechanism of the CARγ

The function domain of the CARγ mainly lies in the intracellular domain, namely the cytosolic Immunoreceptor Tyrosine-based Activation Motifs (ITAMs). The cytosolic Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) in the intracellular domain of the CARγ will be phosphorylated by Src family kinases when the CARγ is stimulated by its ligands S protein. The expression of S protein on the surface of SARS-CoV-2 is actually a strong stimulus of CARγ-macrophages. The activated Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) will expose the SH2 binding domains for the SH2 matching domain. And the SH2 matching domain contains the kinase ZAP70 and the Syk in the T cells and the macrophages respectively. Protein Syk, a phagocytic signaling effector can then active the downstream signaling transduction cascades and initiate the phagocytosis in our CARγ-macrophages eventually.

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
    INCOMPATIBLE WITH RFC[25]
    Illegal NgoMIV site found at 799
    Illegal NgoMIV site found at 958
    Illegal NgoMIV site found at 1024
  • 1000
    INCOMPATIBLE WITH RFC[1000]
    Illegal BsaI.rc site found at 679
    Illegal BsaI.rc site found at 1240
    Illegal BsaI.rc site found at 1249
    Illegal SapI.rc site found at 1197