Killer cell lectin-like receptor subfamily F member 1 (NKp80)–C-type lectin domain family 2 member B (AICL) interaction (NKp80–AICL)

The NKp80–AICL interaction is a significant immune signaling pathway involving the activating receptor Killer cell lectin-like receptor subfamily F member 1 (NKp80) and its ligand, C-type lectin domain family 2 member B (AICL). NKp80 is a homodimeric C-type lectin-like receptor constitutively expressed on nearly all human natural killer (NK) cells and a subset of effector memory CD8+ T cells, where it triggers cytotoxicity and cytokine production via an atypical hemi-ITAM motif (1.1.1, 1.2.4). Its ligand, AICL, is a myeloid-specific protein that is upregulated upon activation by Toll-like receptor (TLR) stimuli and is frequently overexpressed on malignant cells in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) (1.2.2, 1.3.1). This interaction facilitates the immune surveillance of myeloid malignancies and mediates cross-talk between NK cells and monocytes/macrophages during inflammatory responses (1.2.2, 1.4.3). Therapeutic strategies targeting this axis include the development of NKp80-Fc fusion proteins and bispecific immunoligands designed to redirect NK cells toward AICL-positive tumor cells and induce antibody-dependent cellular cytotoxicity (ADCC) (1.3.1, 1.3.2). However, clinical development must address challenges such as NK cell fratricide, which occurs when AICL is induced on NK cells themselves under inflammatory conditions, leading to self-depletion (1.1.2, 1.2.4).

Other names

NKp80–AICL axisKLRF1–CLEC2B interactionNKp80–AICL complexKiller cell lectin-like receptor subfamily F member 1–C-type lectin domain family 2 member B interactionCLEC5C–CLEC2B interaction

Induction of antibody-dependent cellular cytotoxicity (ADCC) and activation of natural killer (NK) cell effector functions through receptor-ligand engagement.