Synthetic Receptor CARγ
Sequence and Features
- 10COMPATIBLE WITH RFC
- 12COMPATIBLE WITH RFC
- 21Illegal XhoI site found at 344
- 23COMPATIBLE WITH RFC
- 25Illegal NgoMIV site found at 952
Illegal NgoMIV site found at 1288
Illegal NgoMIV site found at 1825
Illegal NgoMIV site found at 1891
Illegal NgoMIV site found at 2050
Illegal NgoMIV site found at 2899
Illegal NgoMIV site found at 3058
Illegal AgeI site found at 440
- 1000Illegal BsaI.rc site found at 1168
Illegal BsaI.rc site found at 1432
Illegal BsaI.rc site found at 2779
Illegal BsaI.rc site found at 3340
Illegal BsaI.rc site found at 3349
Illegal SapI.rc site found at 1989
Illegal SapI.rc site found at 3297
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.
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.
More information of this part can be found in FcRγ(BBa_K4040002).
Results of our project
Please find it out in CAR-MERTK(BBa_K4040018).