CD3 epsilon Protein

Dipeptidyl peptidase 4 (DPPIV, also known as CD26) is an approximately 110 kDa serine exopeptidase that releases Xaa-Pro or Xaa-Ala dipeptides from the N-terminus of oligo- and polypeptides. Mature human DPPIV consists of a 6 amino acid (aa) cytoplasmic tail, a 22 aa transmembrane segment, and a 738 aa extracellular domain (ECD) that contains the catalytic active site. DPPIV is expressed as a noncovalent homodimer on the surface of epithelial cells, endothelial cells, and activated lymphocytes, and it can be released by MMP mediated shedding. It regulates immune and endocrine function through the cleavage of multiple chemokines, growth factors, and peptide hormones.CD26/dipeptidyl peptidase (DPP)4 is a membrane-bound protein found in many cell types of the body, and a soluble form is present in body fluids. There is longstanding evidence that various primary tumors and also metastases express CD26/DPP4 to a variable extent. By cleaving dipeptides from peptides with a proline or alanine in the penultimate position at the N-terminus, it regulates the activity of incretin hormones, chemokines and many other peptides. Due to these effects and interactions with other molecules, a tumor promoting or suppressing role can be attributed to CD26/DPP4. DPPIV plays a major role in glucose metabolism. It is responsible for the degradation of incretins such as GLP-1. DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum increased in some neoplasms and decreased in others. DPPIV also binds the enzyme adenosine deaminase specifically and with high affinity. The significance of this interaction has yet to be established.CD3 has five kinds of peptide chains, namely γ chain, δ chain, ε chain, ζ chain and η chain, all of which are transmembrane proteins. The transmembrane region of CD3 molecule connects to the transmembrane region of two peptide chains of TCR through salt bridge, forming the TCR-CD3 complex, which is involved in nervous system development and positive regulation of cell adhesion. CD3 acts upstream of or within several processes, including positive regulation of T cell activation; positive regulation of cytokine production; and regulation of signal transduction. CD3 is located in several cellular components, including dendritic spine; external side of plasma membrane; and immunological synapse. Part of alpha-beta T cell receptor complex. CD3 is expressed in colon and hemolymphoid system. Bispecific therapies targeting CD3, so-called T-cell engagers (TCE), belong to the new spectrum of anti-tumor immunotherapies stimulating T-lymphocytes. TCE are unique constructs targeting the MHC-independent CD3 epsilon subunit (CD3e) and a tumor antigen. Some TCE are in advances development, with promising results targeting CD20 and BSMA in lymphoma and myeloma. These successes have relaunched the development of TCE in solid tumors, bringing mixed results so far (notably in terms of tolerance). Still, TCE pave the way to new immunotherapy in tumors considered to be refractory to inhibitors of immune checkpoints such as prostate cancer or colorectal cancer.