Inhibitory killer-cell immunoglobulin-like receptor and Ly49 receptor (KIR/Ly49)

Inhibitory Killer-cell Immunoglobulin-like Receptors (KIR) and their murine functional counterparts, Ly49 receptors, are essential regulators of Natural Killer (NK) cell surveillance and self-tolerance. These receptors recognize Major Histocompatibility Complex (MHC) class I molecules on the surface of host cells, delivering inhibitory signals through cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that prevent the lysis of healthy self cells [1]. In the context of oncology, tumor cells often exploit this mechanism by maintaining MHC class I expression to suppress NK cell-mediated attack, a process known as immune evasion [2]. Therapeutic strategies, such as the development of the monoclonal antibody lirilumab, aim to block these inhibitory interactions to restore and enhance the anti-tumor effector functions of NK cells [3]. While KIRs are structurally part of the immunoglobulin superfamily and Ly49 receptors are C-type lectin-like proteins, they represent a convergent evolutionary solution for MHC-I-dependent NK cell regulation across species [1]. Citations: [1] Long EO, et al. Annu Rev Immunol. 2013;31:227-58. [2] Purdy AK, Campbell KS. Cancer Biol Ther. 2009;8(23):2211-20. [3] Vey N, et al. Oncoimmunology. 2017;7(2):e1388480.

Other names

CD158Killer cell lectin-like receptor subfamily AKLRNK cell inhibitory receptorMHC class I-binding inhibitory receptor

Antagonism of inhibitory signaling to enhance natural killer cell-mediated cytotoxicity against tumor cells