KIR2DS2

KIR2DS2 is an activating killer-cell immunoglobulin-like receptor of the KIR B haplotype, characterized by its two extracellular Ig domains and short cytoplasmic tail that couples to DAP12 via a charged transmembrane lysine, transmitting activating SYK-dependent signals in NK cells and memory T cells. KIR2DS2 is closely related in sequence to the inhibitory KIR2DL2/3 but, despite sharing their C1-reactive binding-site architecture, KIR2DS2 does not demonstrably bind HLA-C allotypes; instead, its ligands include non-HLA pathogen-derived or stress-induced structures, with reports of binding to viral hemagglutinin-like or Trypanosoma cruzi-derived determinants, and its activating function in chronic infection contributes to immunopathology. Clinically, KIR2DS2 combined with absent HLA-C1 ligands is associated with type 1 diabetes susceptibility, psoriatic arthritis and vascular complications, while in hematopoietic stem-cell transplantation KIR2DS2 may promote graft-versus-leukemia effects. In liver transplantation, KIR2DS2 expression on recipient NK cells correlates with reduced hepatitis C recurrence, illustrating pathogen-directed activation.