Killer cell immunoglobulin-like receptor 2DL5 (KIR2DL5)

Killer cell immunoglobulin-like receptor 2DL5 (KIR2DL5) is an inhibitory receptor primarily expressed on the surface of natural killer (NK) cells and a subset of T cells (Ren et al., 2022). It belongs to the KIR family and is characterized by a unique D0-D2 extracellular domain configuration and a long cytoplasmic tail containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) (Vilches et al., 2000). KIR2DL5 has recently been identified as a high-affinity receptor for poliovirus receptor (PVR, also known as CD155), a ligand it shares with other immune checkpoints like TIGIT and CD96 (Ren et al., 2022). The binding of KIR2DL5 to PVR on target cells, such as tumor cells, triggers inhibitory signaling that suppresses NK cell-mediated cytotoxicity and cytokine production, thereby facilitating immune evasion (Ren et al., 2022). Research indicates that KIR2DL5 acts as a distinct checkpoint that may compensate for the loss of other inhibitory pathways, potentially explaining the limited clinical success of some TIGIT-targeted therapies (Ren et al., 2022). Consequently, blocking the KIR2DL5/PVR axis with monoclonal antibodies is being explored as a novel strategy to enhance antitumor immunity in various solid and hematological malignancies (Ren et al., 2022). Beyond oncology, KIR2DL5 is also implicated in the immune response to viral infections like HIV-1 and the pathogenesis of certain autoimmune and inflammatory conditions (NCBI Gene, 2026).

Other names

KIR2DL5AKIR2DL5BCD158fCD158f1CD158f2Killer cell immunoglobulin-like receptor 2DL5AKiller cell immunoglobulin-like receptor 2DL5B

Blockade of the inhibitory KIR2DL5/PVR (CD155) interaction to restore and enhance natural killer (NK) cell and T cell-mediated immune responses against tumor cells (Ren et al., 2022).