Immunology

PABP is found complexed to the 3-prime poly(A) tail of eukaryotic mRNA and is required for poly(A) shortening, translation initiation, and possibly mRNA export and import. In humans, PABPs are small nuclear isoforms within a conserved gene family of at least 3 functional proteins: PABP1 (PABPC1), inducible PABP (iPABP, or PABPC4), and PABP3 (PABPC3). PABPs are of special interest because due to their high affinity for A-rich mRNA sequences, they are involved in all mRNA-dependent events.

TNF alpha is a multifunctional proinflammatory cytokine that is part of the tumor necrosis factor (TNF) superfamily. It is mainly secreted by macrophages and causes tumor necrosis when injected into tumor -earing mice. It exists as a multimer of two, three, or five noncovalently linked units. TNF alpha is closely related to the 25kD Tumor Necrosis Factor beta (TNF beta, or lymphotoxin), and both proteins share the same receptors and cellular functions. TNF alpha binds and functions through the TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR receptors.

CRLF2 has been reported as an important factor that drives dendritic cell maturation and activation. It was originally shown to participate in the positive selection of regulatory T-cells, maintenance of peripheral CD4+ T-cell homeostasis, and induction of CD4+ T cell-mediated allergic reactions. CRLF2 binds to its receptor with low-affinity; high-affinity binding is facilitated by the presence of IL-7R-alpha to form a functional heteromeric complex.

CCR2 is a receptor for several monocyte chemoattractant proteins (MCP1, MCP3, MCP4) that specifically govern monocyte chemotaxis. CCR2 transduces its downstream signals through increasing intracellular calcium ion levels. For example, MCP1 regulates the monocyte infiltration found in inflammatory diseases such as rheumatoid or the cellular inflammatory response to tumors. CCR2 is also an alternative co-receptor with CD4 for HIV1 infection.

NALP6 belongs to the NLRP family of which function as innate sensors of endogenous and exogenous stress and damage-associated molecular patterns (DAMPs). NLRPs are vital components of the inflammasome which is the cytoplasmic multiprotein complex that coordinates inflammation and cell homeostasis in various type of cells/tissues. NALP6 is one of the newest NLR protein family members and is highly expressed in intestinal epithelium and granulocytes, and to a relatively lower level in T-cells.

This gene encodes the major 3' to 5' DNA exonuclease in human cells. The protein is a non-processive exonuclease that appears to provide proofreading for checkpoint signaling after DNA damage in response to oxidative stress and apoptosis. It is ubiquitously expressed. Trex1 binds to single-stranded DNA coated with replication protein A found at sites of DNA damage, and recruits the ataxia telangiectasia and Rad3 related protein (ATR) checkpoint kinase.

CD73 is a 70kD glycosyl-phosphatidylinositol (GPI)-anchored cell surface molecule that belongs to the 5'-nucleosidase family. It hydrolyzes extracellular nucleotides into membrane permeable nucleosides and is found as both a membrane-bound and soluble molecule. Because it is abundantly expressed on vascular endothelium and some lymphocyte subpopulations, CD73 is a useful lymphocyte differentiation marker. Like many other GPI-anchored molecules, it transmits T-cell activation signals upon ligand engagement.

CD33 is a transmembrane protein that belongs to the sialic acid-binding immunoglobulin-like lectin (siglec) family. These are immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing molecules capable of recruiting the tyrosine phosphatases SHP-1 and SHP-2 to signal assemblies. ITIMs are also used for the ubiquitin-mediated removal of the receptor from cell surfaces. CD33 is expressed on cells of myelomonocytic lineage.

CD16 is a lymphocyte Fc gamma type III low-affinity receptor for IgG and is represented by two similar genes, CD16A (Fc gamma RIII A) and CD16B (Fc gamma RIIIB). CD16A exists as a heterooligomeric polypeptide-anchored form in macrophages and NK cells. CD16B exists as a monomeric glycosylphosphatidylinositol (GPI)-anchored form in neutrophils. CD16 binds IgG in the form of immune complexes or free antibody. It exhibits preferential binding to IgG1 and IgG3 isotypes, with minimal binding of IgG2 and IgG4.

CD86 belongs to the immunoglobulin superfamily of proteins that drive innate and adaptive immune responses. It is an 80kD co-stimulatory molecule for the priming and activation of naive and memory T-cells, respectively. CD86 is expressed on activated B- and T- cells, monocytes/macrophages, dendritic cells, and astrocytes.