Introduction of TNFRSF

Posted by beauty33 on January 23rd, 2019

What is TNFRSF?

Tumor necrosis factor receptor superfamily (TNFRSF) belongs to type I transmembrane glycoprotein, which consists of 29 members, some of which contain death domain (DD). Most of the members bind to the corresponding ligands to form trimers, initiate signal transduction, regulate various biological functions, and participate in a variety of pathological injuries.

The development of TNFRSF

In 1969, researchers first discovered that T lymphocytes can produce a cytotoxic soluble immune molecule, named Lymphotoxin (IT). In 1975, the researchers also found cytokines in macrophage secretion products that can cause hemorrhage and necrosis of tumor cells and tissues, and named them Tumor necrosis factor (TNF). In the 1990s, with the discovery of more and more immunomolecules with similar structures to LT and TNF, these molecules were collectively referred to as Tumor necrosis factor superfamily (TNFSF), and their corresponding receptor molecules were classified as Tumor necrosis factor receptor superfamily (TNFRSF).

The types of TNFRSF

Figure 1. Types of TNFRSF

The first type of receptor contains the death domain (DD) in the tail region of the cytoplasm. Receptors containing death domains, such as Fas-related death domain protein (FADD/MORT1) and TNF-receptor-related death domain protein (TRADD), can be recruited by binding ligands to the corresponding receptors containing death domains, which together constitute so-called death-inducing signal complexes (DISC). These molecules activate caspase and induce apoptosis, but they can also recruit family members of TNF receptor-related factor (TRAF).

The second type of receptor contains one or more TRAF interaction motifs (TIM) in the tail region of the cytoplasm. Activation of these receptors can directly recruit members of the TRAF family and ultimately activate key molecules of multiple signal transduction pathways, such as mitogen-activated protein kinase (MAPK) (such as c-Jun N-terminal kinase JNK), P38 (P38 MAPK), extracellular signal-regulated kinase (ERK), nuclear factor kappa-B inhibitor kinase (IKK) and phosphatidylinositol 3-kinase (PI3K).

The third type of receptor does not contain functional intracellular signal domains or motifs. Although these "bait" receptors are not involved in intracellular signal transduction, they can compete with other two groups of receptors to bind to the corresponding ligands.

The recombinant antibody

Recombinant antibody, also known as genetic engineering antibody, refers to the use of recombinant DNA and protein engineering technology to process, modify and reassemble the genes encoding antibodies according to different needs, and then transfect the antibody molecules expressed by appropriate receptor cells. Recombinant antibody is a generic term for biopharmaceuticals prepared on the platform of high-tech biotechnology such as genetic engineering technology. Procedures for preparation of recombinant antibodies:

1. Objective Gene cloning: According to the structure of recombinant antibody and gene sequence of variable region, primers are designed reasonably, and the target gene is cloned by appropriate cloning method. Variable region genes of heavy chain (VH) and light chain (VH) can be cloned and linked separately, or cloned and linked separately (determined by gene sequence and cloning method).
2. Transforming: The linking products of target genes and expression vectors were transformed into expression vectors, and the appropriate expression vectors were selected according to the selected screening technology.
3. Selection of appropriate screening technology: bacteriophage screening technology: suitable for screening antibody fragment library, the library capacity is relatively large; yeast screening technology: yeast expression system is similar to mammalian cells, so it is often used for the screening and construction of human antibody library; ribosome screening technology: mutant library can be obtained, the library capacity can be large 1014 without the influence of transformation rate.

The recombinant antibody about TNFRSF

Many different types of immune and non-immune cells can produce TNF, including macrophages, T cells, mast cells, granulocytes, natural killer (NK) cells and non-hematopoietic cells, such as fibroblasts, neurons, keratinocytes and smooth muscle cells. TNF inhibitors are the most successful biological agents. Its clinical efficacy has been fully demonstrated in alleviating inflammation associated with some autoimmune diseases. Therefore, the therapeutic potential of cytokines related to TNF superfamily structure has attracted much attention.

The development of recombinant antibody has brought the antibody preparation technology into a new era, especially the progress of drug antibody library, solved the development of human antibody, promoted the development of various excellent antibodies and antibody fusion proteins with multiple functions. It can be foreseen that the development of recombinant antibody is entering a new peak.