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CD74 (HLA class II histocompatibility antigen gamma chain isoform b), is a transmembrane protein (on antigen presenting cells) which is the invariant chain that chaperones MHC class IIdimers from the endoplasmic reticulum to the cell surface. CD74 is expressed by cells of both T lymphocyte and Blymphocyte lineages. CD74 upregulated in several cancers and is also expressed by non immune cells during inflammation. Diseases related with CD74 include thymic epithelial neoplasm and gastroduodenitis. Among its related super-pathways are Immune System and Immune response Antigen presentation by MHC class II. In addition CD74 functions as cell surface receptor for the cytokine MIF.

KLRB1 has an inhibitory role on natural killer (NK) cells cytotoxicity which are lymphocytes who facilitate cytotoxicity and secrete cytokines subsequent to immune stimulation. Some genes of the C-type lectin superfamily, like the rodent NKRP1 family of glycoproteins, are expressed by NK cells and take part in NK cell function regulation. KLRB1 holds an extracellular domain with a few characteristic motifs of C-type lectins, a transmembrane domain, and a cytoplasmic domain. Due to its external C terminus KLRB1 is considered to be a type II membrane protein.

NCR2 is a member of the natural cytotoxicity receptor (NCR) family and holds 1 immunoglobulin-like (Ig-like) domain. NCR2 cooperates with TYROBP/DAP12 and is specifically expressed by activated NK cells and by in vitro cultured TCRg/d lymphoid cells. NCR2 is a cytotoxicity-activating receptor which induces the amplified efficiency of activated natural killer (NK) cells to mediate tumor cell lysis.

CD45 leukocyte common antigen (LCA) belongs to the family of at least four isoforms of membrane glycoproteins (220, 205, 190, 180kDa) expressed on hematopoietic cell lines but absent on non-hematopoietic cell lines, normal and malignant non-hematopoietic tissues. The intracellular portion of these molecules has protein phosphatase activity and is involved in regulation of transmembrane signals.

KLRD1, also known as Killer Cell Lectin Like Receptor D1, is expressed on the surface of natural killer cells in the innate immune system. KLRD1 functions as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. KLRD1 can create disulfide-bonded heterodimer with NKG2 family members. CD94 & NKG2 complex interacts with (HLA)-E, Human Leukocyte Antigen on target cells on the surface of natural killer cells.

IFN-beta has antiviral, antibacterial and anticancer activities.

Leucine Rich Repeats And Immunoglobulin Like Domains 1 or LRIG1 is a protein, acting as is a pan-negative regulator of EGFR signal transduction. When studied along with ErbB proteins and Met kinase, LRIG1 was found to have regulation activities such as ubiquitination and lysosomal degradation increment of the receptors. Therefore, LRIG1 acts as a suppressor for tumors via cell proliferation control via negative regulation of tyrosine kinase receptors that belongs to the EGF protein family. LRIG1 expression is downregulated in cancer, and acts a prognostic tool for cancer development.

Killer-cell immunoglobulin-like receptors (KIRs), are a family of cell surface glycoproteins found on Natural Killer (NK) Cells, which are important cells of the immune system. They control the killing function of these cells by interacting with MHC class I molecules, which are expressed on all cell types. This interaction allows them to identify virally infected cells or tumor cells that have a distinctive low level of Class I MHC on their surface. The majority of KIRs are inhibitory, which means that their recognition of MHC suppresses the cytotoxic activity of their NK cell. Only a limited number of KIRs have the capacity to activate cells.
The KIR genes are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). KIR molecules are extremely polymorphic, meaning their gene sequences differ significantly between individuals, so that different individuals have different arrays/repertoires of KIR genes.
The KIR proteins are categorized by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM). Whereas KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals.
KIR2DL1 is an inhibitory Killer Cell Ig-like Receptor (KIR, previously called p58 KIR, p58.1, cl-42, NKAT1, or KIR-K6), which recognizes class I MHC molecules (HLA-Cw2, -Cw4, -Cw5, and Cw6). The extracellular domain of KIR2DL1 was over expressed as insoluble protein aggregates (inclusion bodies).

IL-28A is distantly related to type I IFNs and the IL-10 family. Expression of IL-28A is induced by viral infection which interacts with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha. IL-28A exhibits common features with type I IFNs such as antiviral activity, antiproliferative activity and in vivo antitumour activity.
IL-28A acts similarly to IFNs, but is less effective generally and has activity in a more limited range of cell lines. IFN-ambda 1, IFN-lambda 2 and IFN-lambda 3 are closely positioned genes on human chromosome 19.
IL-28A induces ELR(-) CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-gamma-independent manner.
IL-28A is able to generate tolerogenic DCs, an activity that could thwart IFN-beta functions. IL-28A produced in response to viral infection, activates both monocytes and macrophages producing a restricted panel of cytokines and therefore is an important factor in activating innate immune responses at the site of viral infection.

IRF7 belongs to the interferon regulatory transcription factor (IRF) family. IRF7 plays a role in the transcriptional activation of virus-inducible cellular genes, including interferon beta chain genes. Inducible expression of IRF7 is largely restricted to lymphoid tissue.

Glutathione reductase (GSR) belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. The GSR enzyme is a homodimeric flavoprotein and has a role in maintaining glutathione (GSH) in its reduced form by catalyzing the reduction of glutathione disulfide (GSSG): GSSG + NADPH + H+ ->2GSH + NADP+. In the majority of eukaryotic cells, GSR upholds the ratio of [GSH] / [GSSG], and partakes in quite a few critical functions such as the detoxification of reactive oxygen species as well as protein and DNA biosynthesis.

CCL23 (MIP-3) is a ligand for the CCR1chemokine receptor. CCL23 is one of several cytokine genes clustered on the q-arm of chromosome 17, in a locus containing several other CC chemokines. MIP-3 chemoattracts monocytes, resting T-lymphocytes and neutrophils, but not activated lymphocytes. Furthermore, it was shown that MIP-3 inhibits colony formation of bone marrow myeloid immature progenitors. MIP-3 is mainly expressed in lung and liver tissue, but can be also found in bone marrow and placenta, as well as in some cell lines of myeloid origin.
Alternative splicing of the CCL23 gene produces 2 mRNAs which encode a short (CK?8) and a long (CK?81) isoform of the MIP-3. CK?8 cDNA encodes a 120 amino acid residue precursor protein with a putative 21 a.a. residue signal peptide which is cleaved to generate a 99 a.a. residue mature CK?8 (a.a. 22-120). Further N-terminal processing of the 99 a.a. residue variant can produce a 75 a.a. residue CK?8 (a.a. 46-120) which is considerably more active than the 99 a.a. residue variant.
MIP-3 may be involved in the malignant progression of certain human cancer cells which overexpress ErbB2 through the transactivation of ErbB2 tyrosine kinase. MIP-3 may also be involved in angiogenesis via upregulation of matrix metalloproteinase MMP-2 expression.

CD40L or CD154 is a membrane glycoprotein and differentiation antigen expressed on the surface of T-cells. The CD40 ligand stimulates B-cell proliferation and secretion of all immunoglobulin isotypes in the presence of cytokines . CD40 ligand has been shown to induce cytokine production and tumoricidal activity in peripheral blood monocytes. It also costimulates proliferation of activated T-cells and this is accompanied by the production of IFN-gamma , TNF-alpha , and IL2 .

Interleukin-1b is produced by activated macrophages, IL-1B stimulates thymocyte proliferation by inducing il-2 release, b-cell maturation and proliferation, and fibroblast growth factor activity. IL1B proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells. IL-1b is an inflammatory cytokine which modulates angiogenesis by interacting directly with vascular endothelial cells & increasing the production of proangiogenic factors through paracrine control. IL-1 beta stimulates endothelial cell migration and proliferation, adhesion-molecule expression, inflammatory mediator production, and leukocyte recruitment. IL1B is essential for tumor growth, metastasis, and angiogenesis in quite a few animal models.

Interferon Alpha And Beta Receptor, also known IFNAR1, belongs to the class II cytokine receptor family. IFNAR1 protein forms one of the two chains of a receptor for interferons alpha as well as beta. IFNAR1 binds and activates the receptor which stimulates Janus protein kinases, which in turn phosphorylate some proteins, including STAT1 & STAT2. Furthermore, IFNAR1 also functions as an antiviral factor.

CD209 (a member of the C-typelectin family) is Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) andtakes part in initiation of primary immune response.CD209has a high affinity for theICAM3 molecule and binds various microorganisms by recognizing high-mannose-containing glycoproteins ontheir envelopes and especially functions as receptor for several viruses such as HIV and Hepatitis C. Along with other C-typelectins, CD209is involved in recognition of tumors by dendritic cells.CD209also initiatesnatural immunity bymodulating toll-like receptors.

Chemokine (C-X-C motif) ligand 10 (CXCL10) is a small cytokine belonging to the CXC chemokine family. CXCL10 is secreted by several cell types in response to IFN-?. These cell types include monocytes, endothelial cells and fibroblasts. CXCL10 has been attributed to several roles, such as chemoattraction for monocytes and T cells, promotion of T cell adhesion to endothelial cells, antitumor activity, and inhibition of bone marrow colony formation and angiogenesis. The gene for CXCL10 is located on human chromosome 4 in a cluster among several other CXC chemokines. This chemokine elicits its effects by binding to the cell surface chemokine receptor CXCR3. The three-dimensional crystal structure of this chemokine has been determined under 3 different conditions to a resolution of up to 1.92A.

Killer-cell immunoglobulin-like receptors (KIRs), are a family of cell surface glycoproteins found on Natural Killer (NK) Cells, which are important cells of the immune system. They control the killing function of these cells by interacting with MHC class I molecules, which are expressed on all cell types. This interaction allows them to identify virally infected cells or tumor cells that have a distinctive low level of Class I MHC on their surface. The majority of KIRs are inhibitory, which means that their recognition of MHC suppresses the cytotoxic activity of their NK cell. Only a limited number of KIRs have the capacity to activate cells. The KIR genes are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). KIR molecules are extremely polymorphic, meaning their gene sequences differ significantly between individuals, so that different individuals have different arrays/repertoires of KIR genes. The KIR proteins are categorized by the number of

CD163 is an acute phase-regulated receptor which participates in the removal and endocytosis of hemoglobin/haptoglobin complexes by macrophages and thus keeps tissues from free hemoglobin-mediated oxidative damage. Furthermore, CD163 partakes in the uptake and recycling of iron, through endocytosis of hemoglobin/haptoglobin and ensuing breakdown of heme. In addition, CD163 binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent way. CD163 demonstrates greater affinity for complexes of hemoglobin and multimeric haptoglobin of HP-1F phenotype than for complexes of hemoglobin and dimeric haptoglobin of HP-1S phenotype. Moreover, CD163 stimulates a cascade of intracellular signals which involves tyrosine kinase-dependent calcium recruitment, inositol triphosphate formation and secretion of IL-6 & CSF-1.

IL-7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.

IFN-alpha is produced by macrophages, IFN-alpha has antiviral activities and stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.

CD8 is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. CD8 acts as a co-receptor, and the T-cell receptor on the T lymphocyte recognize antigen displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional CD8 is either a homodimer composed of two alpha chains, or a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains.
CD8 identifies cytotoxic/suppressor t-cells that interact with MHC class I bearing targets. CD8 is thought to play a role in the process of t-cell mediated killing. CD8 alpha chains bind to class-I MHC molecules alpha-3 domains.