SIRPalpha

SIRPalpha, also known as CD72, is a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family of proteins. It is a type I transmembrane protein that functions as a receptor for sialic acid, a carbohydrate component found on the surface of many cells. SIRPalpha is primarily expressed on the surface of natural killer (NK) cells, where it plays a crucial role in immune regulation.

The primary function of SIRPalpha is to inhibit the activation of NK cells. It achieves this by binding to sialic acid residues on the surface of target cells, such as cancer cells or infected cells. This binding prevents the NK cells from recognizing and attacking these target cells, thereby maintaining immune homeostasis. SIRPalpha also has a role in the regulation of T cell activation and differentiation.

SIRPalpha is encoded by the SIGLEC7 gene, which is located on chromosome 19 in humans. It is a single-pass transmembrane protein with a large extracellular domain that contains multiple sialic acid-binding sites. The intracellular domain of SIRPalpha contains an immunoreceptor tyrosine-based inhibition motif (ITIM), which is responsible for the inhibitory signaling of the receptor.

SIRPalpha has been the subject of extensive research due to its potential as a therapeutic target in cancer and autoimmune diseases. Modulating SIRPalpha signaling could enhance the efficacy of NK cell-based therapies for cancer, while also providing a new approach to treating autoimmune disorders. However, the complex regulation of SIRPalpha signaling and its role in immune homeostasis make it a challenging target for therapeutic intervention.