Difference between revisions of "Part:BBa K4040003"

Revision as of 06:46, 5 October 2021

Intracellular Domain of CD3 zeta chain

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]

Usage and Biology

T-cell surface glycoprotein CD3 zeta chain is part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways [1,2].

CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme [2].

It plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN) (By similarity).

Figure 1. Structure of CD3 zeta chain.

Background and detail description

Used in the construction of CAR-T cells

The synthetic receptors were constructed to contain an scFv derived from an antibody recognizing the virus spike protein, CR3022, which has been reported to bind with the receptor-binding domain of the SARS-CoV-2 S glycoprotein with high affinity, and the CD8 transmembrane domain present in the aCD19 CAR for T cells (12). For the cytoplasmic domains, we used the common g subunit of Fc receptors (CARg), MEGF10 (CARMEGF10), MERTK (CARMERTK) and CD3z (CARz) in our study. These cytoplasmic domains are capable of promoting phagocytosis by macrophages. More details and experimental results can be found in CAR-CD3 zeta(BBa_K4040017)

Used in the construction of CAR-Macrophages cells

References

[1]Barber EK, Dasgupta JD, Schlossman SF, Trevillyan JM, Rudd CE. The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Proc Natl Acad Sci U S A. 1989 May;86(9):3277-81. doi: 10.1073/pnas.86.9.3277. PMID: 2470098; PMCID: PMC287114.

[2]Iwashima M, Irving BA, van Oers NS, Chan AC, Weiss A. Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. Science. 1994 Feb 25;263(5150):1136-9. doi: 10.1126/science.7509083. PMID: 7509083.

@@ Line 14: / Line 14: @@
 ===Used in the construction of CAR-T cells===
 The synthetic receptors were constructed to contain an scFv derived from an antibody recognizing the virus spike protein, CR3022, which has been reported to bind with the receptor-binding domain of the SARS-CoV-2 S glycoprotein with high affinity, and the CD8 transmembrane domain present in the aCD19 CAR for T cells (12). For the cytoplasmic domains, we used the common g subunit of Fc receptors (CARg), MEGF10 (CARMEGF10), MERTK (CARMERTK) and CD3z (CARz) in our study. These cytoplasmic domains are capable of promoting phagocytosis by macrophages. More details and experimental results can be found in <b>CAR-CD3 zeta</b>(<partinfo>BBa_K4040017</partinfo>)
+===Used in the construction of CAR-Macrophages cells===
 ===References===
 [1]Barber EK, Dasgupta JD, Schlossman SF, Trevillyan JM, Rudd CE. The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Proc Natl Acad Sci U S A. 1989 May;86(9):3277-81. doi: 10.1073/pnas.86.9.3277. PMID: 2470098; PMCID: PMC287114.