HLA-F and MHC-I open conformers are ligands for natural killer cell receptor KIR3DL2.

Abstract Killer Immunoglobulin-like receptors (KIR) are innate immune receptors expressed by NK and T cells classically associated with the detection of missing-self through loss of their respective MHC ligand. Some KIR specificities for allelic classical class I MHC (MHC-I) have been described, while other KIR receptor-ligand relationships, including those associated with non-classical MHC-I, have yet to be clearly defined. We report here that KIR3DL2 and the non-classical antigen HLA-F, expressed as a free form devoid of peptide, physically and functionally interact. We further extend those results to include classical MHC-I open conformers as ligands, defining new allelic relationships with KIR3DL2 and MHC-I. The data collectively suggest a broader, previously unrecognized interaction between MHC-I open conformers - with HLA-F as a prototypical example - and KIR receptors, acting in an immunoregulatory capacity centered on the inflammatory response.