Interleukin-2 receptor (IL-2R) also known as High-affinity IL-2 receptor subunit beta, IL-2 receptor subunit beta, and IL-2RB, is involved in T cell-mediated immune responses. CD122/IL-2RB is present in 3 forms concerning the ability to bind interleukin 2. The low-affinity form is a monomer of the alpha subunit and is not involved in signal transduction. The intermediate affinity form consists of an alpha/beta subunit heterodimer, while the high-affinity form consists of an alpha/beta/gamma subunit heterotrimer. Both the intermediate and high-affinity forms of CD122/IL-2RB are involved in receptor-mediated endocytosis and transduction of mitogenic signals from interleukin 2. CD122/IL-2RB expression was restricted to the earliest B220+ cells (CD43+CD24-, prepro B cells, fraction A) that proliferate vigorously to IL-2 in the absence of any stromal cells, but not to IL-15. The high-affinity form of this receptor is expressed on activated T lymphocytes, activated B lymphocytes, and activated macrophages. CD122/IL-2RB plays a role in regulating normal lymphocyte development.
The IL-7 receptor (IL-7R) is comprised of two protein subunits, CD127/IL-7Rα (IL-7Ralpha) and the common gamma chain (CD132), which is the major signaling component for several cytokines including IL-2, IL-4, IL-9, IL-15, and IL-21. CD127/IL-7Rα is a transmembrane protein belonging to the cytokine receptor homology class 1 (CRH1) and is expressed by a wide variety of cells including immature B cells, thymic natural killer cells, bone marrow stromal cells, and T cells. On its own, CD127/IL-7Rα functions as a receptor for two cytokine receptor complex signaling cascades: IL-7 and thymic stromal lymphopoietin (TSLP). IL-7 signaling contributes to T cell development and homeostasis whereas TSLP receptor signaling contributes to dendritic cell activation and B cell development. IL-7 signaling is an essential component in regulating the homeostasis of naive and memory T cells as differential expression of CD127/IL-7Rα is observed on naive and activated T cells, which occurs following TCR activation. Specifically, CD127/IL-7Rα expression is downregulated on activated T cells and the subsequent re-expression of CD127/IL-7Rα on these cells is indicative of cells that will differentiate into memory T cells.
Interleukin-18-binding protein (IL-18BP) is a constitutively expressed and secreted protein. IL-18BP is a cytokine receptor that belongs to the interleukin 1 receptor family. This receptor specifically binds interleukin 18 (IL18) and is essential for IL18 mediated signal transduction. IFN-alpha and IL12 are reported to induce the expression of this receptor in NK and T cells. This gene along with four other members of the interleukin 1 receptor family , including IL1R2 , IL1R1 , ILRL2 (IL-1Rrp2) , and IL1RL1 (T1/ST2) , form a gene cluster on chromosome 2q. The adjacently located family members IL18 Receptor 1 (IL18R1) and IL18 receptor accessory protein (IL18RAP) may also be important in the development of asthma and atopy. IL-18 binding protein (IL-18BP) was only moderately elevated , resulting in a high level of biologically active free IL-18 in HPS. A severe IL-18/IL-18BP imbalance results in Th-1 lymphocyte and macrophage activation , which escapes control by NK-cell cytotoxicity and may allow for secondary HPS in patients with underlying diseases.
Interleukin 18 binding protein (IL-18BP) is a physiological inhibitor that acts through binding to the receptor-binding site of IL-18. IL-18 stimulates INF-γ, which then stimulates 18BP production via NF-κB. The interaction between IL-18 and IL-18BP has a significant role in the inflammation process. IL-18 BPs have four isoforms, a, b, c and d, which are spliced by different ways. The IL-18 BP isoforms a and c each contain one immunoglobulin (Ig)-like C2-type domain which is essential to the binding and neutralizing properties of the binding proteins. The IL-18 BP isoforms b and d lack a complete Ig domain. The expression of IL-18 and the IL-18BP are indentified in immune tissues such as the spleen, but also in nonimmune cells including keratinocytes.
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