HLA-F
Description
The HLA-F (major histocompatibility complex, class I, F) is a protein-coding gene located on chromosome 6.
HLA-F, encoded by the HLA-F gene, is a non-classical MHC class I molecule. It exists as an empty intracellular molecule with a non-classical heavy chain anchored to the membrane and forming a heterodimer with a β-2 microglobulin light chain. HLA-F is located in the endoplasmic reticulum and Golgi apparatus and shows limited polymorphisms. The HLA-F gene produces numerous transcript variants and isoforms. Its pathways include IFN-gamma signaling, CDK-mediated phosphorylation, and removal of the Saccharomyces cerevisiae Cdc6 protein, crucial for DNA replication. The Major Histocompatibility Complex (MHC), also known as the Human Leukocyte Antigen (HLA) complex in humans, is a group of cell surface proteins encoded by a cluster of genes called the HLA locus on chromosome 6. The HLA locus contains over 140 genes, categorized into class I, II, and III. HLA-A, B, and C are classical class I genes, while HLA-E, F, and G are non-classical class I genes.
HLA-F, also known as CDA12, HLA F antigen, Leukocyte antigen F, and MHC class I antigen F, is a non-classical major histocompatibility class Ib molecule that plays a role in immune surveillance, immune tolerance, and inflammation. It exists in two forms: a heterotrimeric complex with beta-2 microglobulin (B2M) and a peptide (peptide-bound HLA-F-B2M), and an open conformer (OC) devoid of peptide and B2M (peptide-free OC). In complex with B2M, HLA-F presents non-canonical self-peptides with post-translational modifications, particularly phosphorylated self-peptides. Peptide-bound HLA-F-B2M acts as a ligand for LILRB1 inhibitory receptor, a key player in maternal-fetal tolerance. Peptide-free OC acts as a ligand for KIR3DS1 and KIR3DL2 receptors. Interaction with activating KIR3DS1 receptor on NK cells triggers NK cell degranulation and anti-viral cytokine production. Interaction with KIR3DL2 receptor inhibits NK and T cell effector functions. HLA-F may interact with other MHC class I OCs to cross-present exogenous viral, tumor, or minor histocompatibility antigens to cytotoxic CD8+ T cells, triggering effector and memory responses. It may also play a role in inflammatory responses in the peripheral nervous system. Through interaction with KIR3DL2, it may protect motor neurons from astrocyte-induced toxicity.
HLA-F is also known as CDA12, HLA-5.4, HLA-CDA12, HLAF.
