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). Forms a heterotrimer with B2M and a self-peptide (PubMed:28636952). Binds a diverse number of peptides ranging from 7 to more than 30 amino acids (PubMed:28636952). Peptide-bound HLA-F-B2M interacts with LILRB1 and LILRB2 but not with KIR3DS1 or KIR3DL2; this interaction is direct (PubMed:28636952, PubMed:11169396). The OC form interacts with KIR3DS1, KIR2DS4 and KIR3DL2; this interaction is direct (PubMed:28636952, PubMed:27455421, PubMed:24018270). Interacts with TAP1-TAP2 complex and CALR; this interaction is required for appropriate folding and peptide loading (PubMed:10605026, PubMed:11169396). Interacts with the coat protein complex II and 14-3-3 proteins; these interactions likely control the anterograde ER-to-Golgi transport of HLA-F (PubMed:16709803). HLA-F-B2M complex interacts with the heavy chain of other MHC class I molecules including HLA-A and HLA-E; this interaction may regulate the intracellular trafficking and the stability of peptide-free MHC class I OCs (PubMed:20483783). For cross-presentation transits from the cell surface through endosomal pathway to lysosomes, where the peptide is generated from internalized exogenous antigen. Expressed in resting B cells (at protein level). Expressed in secondary lymphoid organs rich in B and T cells such as the tonsils, spleen, and thymus (at protein level) (PubMed:10605026, PubMed:11169396). Expressed in the endothelial cells of the tonsils (PubMed:11169396). Expressed on activated lymphoid cells including B cells, NK cells, CD4+ T cells and memory T cells (at protein level) (PubMed:27455421, PubMed:20865824). Expressed in motor neurons of spinal cord (PubMed:26928464). Expressed in fetal liver (at protein level) (PubMed:10605026). Expressed in placenta villous mesenchyme, cytotrophoblast, syncytiotrophoblast and invasive extravillous trophoblast (at protein level) (PubMed:28185362). Up-regulated in CD4+ T cells upon stimulation via TCR and upon HIV-1 infection. N-glycosylated. Belongs to the MHC class I family. Extended N-terminus.