Jurkat cells are an immortalized line of human T lymphocyte cells that are used to study acute T cell leukemia, T cell signaling, and the expression of various chemokine receptors susceptible to viral entry, particularly HIV. [1] Jurkat cells can, upon stimulation by phytohaemagglutinin (PHA) or other stimulants such as phorbol 12-myristate 13-acetate (PMA or simply phorbol), express interleukin 2, and are used in research involving the susceptibility of cancers to drugs and radiation. However in the general case chronic phytohaemagglutinin kills Jurkat cells, though Jurkat clones can be devised which resist PHA-induced killing. The object of the system is that Jurkat cells can react to a signal and their expression can be measured. Jurkat cells with elements missing or knocked out can then provide a basis for examining the importance of that element on the expression of interleukin 2.
The Jurkat cell line (originally called JM) was established in the mid-1970s from the peripheral blood of a 14-year-old boy with T cell leukemia. [2] [3] Different derivatives of the Jurkat cell line that have been mutated to lack certain genes can now be obtained from cell culture banks. [4]
Jurkat E6-1 cells have been found to produce a xenotropic murine leukemia virus (X-MLV) (referred to as XMRV) that could potentially affect experimental outcomes. There is no evidence that this virus can infect humans. This infection may also change the virulence and tropism of the virus by way of phenotypic mixing and/or recombination. [5]
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.
Interleukins (ILs) are a group of cytokines that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related proteins.
Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically they cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. Superantigens act by binding to the MHC proteins on antigen-presenting cells (APCs) and to the TCRs on their adjacent helper T-cells, bringing the signaling molecules together, and thus leading to the activation of the T-cells, regardless of the peptide displayed on the MHC molecule. SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system. Compared to a normal antigen-induced T-cell response where 0.0001–0.001% of the body's T-cells are activated, these SAgs are capable of activating up to 20% of the body's T-cells. Furthermore, Anti-CD3 and Anti-CD28 antibodies (CD28-SuperMAB) have also shown to be highly potent superantigens.
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR.
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell-antigen interactions.
Tyrosin-protein kinase Lck is a 56 kDa protein that is found inside lymphocytes and encoded in the human by the LCK gene. The Lck is a member of Src kinase family (SFK) and is important for the activation of T-cell receptor (TCR) signaling in both naive T cells and effector T cells. The role of Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets. It seems that in mice, in the effector memory T cell (TEM) population, more than 50% of Lck is present in a constitutively active conformation, whereas less than 20% of Lck is present as active form in central memory T cells. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.
ZAP-70 is a protein normally expressed near the surface membrane of lymphocytes. It is most prominently known to be recruited upon antigen binding to the T cell receptor (TCR), and it plays a critical role in T cell signaling.
NKG2 also known as CD159 is a receptor for natural killer cells. There are 7 NKG2 types: A, B, C, D, E, F and H. NKG2D is an activating receptor on the NK cell surface. NKG2A dimerizes with CD94 to make an inhibitory receptor (CD94/NKG2).
The Linker for activation of T cells, also known as linker of activated T cells or LAT, is a protein involved in the T-cell antigen receptor signal transduction pathway which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.
T-cell surface glycoprotein CD3 zeta chain also known as T-cell receptor T3 zeta chain or CD247 is a protein that in humans is encoded by the CD247 gene.
T-cell surface glycoprotein CD3 gamma chain is a protein that in humans is encoded by the CD3G gene.
Protein kinase C theta (PKC-θ) is an enzyme that in humans is encoded by the PRKCQ gene. PKC-θ, a member of serine/threonine kinases, is mainly expressed in hematopoietic cells with high levels in platelets and T lymphocytes, where plays a role in signal transduction. Different subpopulations of T cells vary in their requirements of PKC-θ, therefore PKC-θ is considered as a potential target for inhibitors in the context of immunotherapy.
CD3e molecule, epsilon also known as CD3E is a polypeptide which in humans is encoded by the CD3E gene which resides on chromosome 11.
Protein kinase C eta type is an enzyme that in humans is encoded by the PRKCH gene.
Serine/threonine-protein kinase D2 or PKD2 is an enzyme that in humans is encoded by the PRKD2 gene.
Interleukin-2 receptor subunit beta is a protein that in humans is encoded by the IL2RB gene. Also known as CD122; IL15RB; P70-75.
Interleukin-28 receptor is a type II cytokine receptor found largely in epithelial cells. It binds type 3 interferons, interleukin-28 A, Interleukin-28B, interleukin 29 and interferon lambda 4. It consists of an α chain and shares a common β subunit with the interleukin-10 receptor. Binding to the interleukin-28 receptor, which is restricted to select cell types, is important for fighting infection. Binding of the type 3 interferons to the receptor results in activation of the JAK/STAT signaling pathway.
The interleukin-2 receptor alpha chain is a protein involved in the assembly of the high-affinity interleukin-2 receptor, consisting of alpha (IL2RA), beta (IL2RB) and the common gamma chain (IL2RG). As the name indicates, this receptor interacts with interleukin-2, a pleiotropic cytokine which plays an important role in immune homeostasis.
Nef is a small 27-35 kDa myristoylated protein encoded by primate lentiviruses. These include Human Immunodeficiency Viruses and Simian Immunodeficiency Virus (SIV). Nef localizes primarily to the cytoplasm but also partially to the Plasma membrane (PM) and is one of many pathogen-expressed proteins, known as virulence factors, which function to manipulate the host's cellular machinery and thus allow infection, survival or replication of the pathogen. Nef stands for "Negative Factor" and although it is often considered indispensable for HIV-1 replication, in infected hosts the viral protein markedly elevates viral titers.
Interleukin-7 receptor subunit alpha (IL7R-α) also known as CD127 is a protein that in humans is encoded by the IL7R gene.