Part:BBa_K4040002

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.

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