KLRG1

Killer cell lectin-like receptor G1 (KLRG1), also known as CLEC15A, is an inhibitory receptor predominantly expressed on natural killer (NK) cells and antigen-experienced T-cell subsets. It binds E-cadherin on epithelial and tumor cells, transmitting inhibitory signals via immunoreceptor tyrosine-based inhibitory motifs (ITIMs) to suppress lymphocyte activation and proliferation. KLRG1 engagement modulates T-cell exhaustion in chronic viral infections and cancer, impacting immune surveillance. This receptor is implicated in age-related immune dysfunction and tumor immune evasion, with elevated expression observed in melanoma and chronic lymphocytic leukemia. Therapeutic strategies targeting KLRG1-E-cadherin interactions are under preclinical investigation, including blocking antibodies to reverse T-cell exhaustion and bispecific molecules redirecting NK cells against E-cadherin+ tumors. Its dual role in immune regulation makes KLRG1 a nuanced target for immunotherapy development.