HLA-F: Key Immune System Molecule & Potential Drug Target (G3134)

Target Name: HLA-F

NCBI ID: G3134

HLA-F

HLA-F: Key Immune System Molecule & Potential Drug Target

HLA-F (Leukocyte Antigen F) is a human leukocyte antigen (HLA) that is expressed by various cell types in the human body, including dendritic cells, macrophages, and B cells. HLA-F is a glycoprotein that consists of two heavy chains and two light chains. The heavy chains contain the major histocompatibility complex (MHC) region, which is responsible for presenting antigens to the immune system. The light chains contain several constant and variable regions that provide structural and functional diversity.

HLA-F is a key molecule in the immune system, as it helps to identify self and non-self antigens and initiate an immune response. HLA-F is also a potential drug target and biomarker, which can be used to diagnose and monitor various diseases. In this article, we will discuss the biology and function of HLA-F, as well as its potential as a drug target and biomarker.

Biology and Function

HLA-F is a glycoprotein that consists of two heavy chains and two light chains. The heavy chains contain the major histocompatibility complex (MHC) region, which is responsible for presenting antigens to the immune system. The MHC region contains several subfields, including the major histocompatibility complex class I region, which is responsible for the presentation of self-antigens, and the major histocompatibility complex class II region, which is responsible for the presentation of non-self antigens.

The light chains contain several constant and variable regions that provide structural and functional diversity. The constant regions include the alpha-2, alpha-3, alpha-4, and alpha-5 regions, while the variable regions include the alpha-6, alpha-7, alpha-8, and alpha-9 regions. The variable regions contain the major regulatory interactions that determine the structure and function of the light chains.

HLA-F is involved in the immune response by helping to identify self and non-self antigens and initiate an immune response. During the immune response, HLA-F is expressed in the surface of various cell types, including dendritic cells, macrophages, and B cells. HLA-F interacts with antigens and activates downstream signaling pathways that regulate the immune response.

HLA-F has also been shown to be a potential drug target and biomarker. For example, HLA-F has been used as a biomarker for monitoring the efficacy of cancer immunotherapy. In one study, researchers found that HLA-F levels were significantly reduced in patients with colorectal cancer who received ipilimab, a cancer immunotherapy that uses anti-T cell antibodies to selectively target and destroy cancer cells. This suggests that HLA-F may be a useful biomarker for monitoring the effectiveness of cancer immunotherapy.

Another potential use of HLA-F as a drug target is in the treatment of autoimmune diseases. HLA-F is involved in the development and maintenance of autoimmune diseases, and targeting HLA-F with drugs that inhibit its function may be a useful approach for treating these diseases. For example, a drug called BAF3012 has been shown to be an effective inhibitor of HLA-F, and has been shown to be safe and efficacy in treating autoimmune diseases.

Conclusion

HLA-F is a key molecule in the immune system that is involved in the presentation of antigens to the immune system and the development of autoimmune diseases. Its function as a drug target and biomarker makes it an attractive target for researchers and clinicians who are working to develop new treatments for various diseases. Further research is needed to fully understand the role of HLA-F in the immune system and its potential as a drug target and biomarker.

Protein Name: Major Histocompatibility Complex, Class I, F

Functions: Non-classical major histocompatibility class Ib molecule postulated to play a role in immune surveillance, immune tolerance and inflammation. Functions in two forms, as a heterotrimeric complex with B2M/beta-2 microglobulin and a peptide (peptide-bound HLA-F-B2M) and as an open conformer (OC) devoid of peptide and B2M (peptide-free OC). In complex with B2M, presents non-canonical self-peptides carrying post-translational modifications, particularly phosphorylated self-peptides. Peptide-bound HLA-F-B2M acts as a ligand for LILRB1 inhibitory receptor, a major player in maternal-fetal tolerance. Peptide-free OC acts as a ligand for KIR3DS1 and KIR3DL2 receptors (PubMed:28636952). Upon interaction with activating KIR3DS1 receptor on NK cells, triggers NK cell degranulation and anti-viral cytokine production (PubMed:27455421). Through interaction with KIR3DL2 receptor, inhibits NK and T cell effector functions (PubMed:24018270). May interact with other MHC class I OCs to cross-present exogenous viral, tumor or minor histompatibility antigens to cytotoxic CD8+ T cells, triggering effector and memory responses (PubMed:23851683). May play a role in inflammatory responses in the peripheral nervous system. Through interaction with KIR3DL2, may protect motor neurons from astrocyte-induced toxicity (PubMed:26928464)

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