Invariant surface glycoprotein (ISG)

Invariant surface glycoproteins (ISGs) are a family of type I transmembrane proteins found on the surface of Trypanosoma brucei, the parasite responsible for African trypanosomiasis (sleeping sickness). Unlike the dominant variant surface glycoproteins (VSGs), ISGs do not undergo antigenic variation and are expressed exclusively in the mammalian bloodstream form of the parasite (Makarov et al., 2023; Macleod et al., 2022). The two most prominent members, ISG65 and ISG75, serve as critical interfaces between the parasite and the host environment. ISG65 functions as a receptor for complement component C3b, helping the parasite evade the host's innate immune system by inhibiting complement-mediated clearance (Cook et al., 2024; Macleod et al., 2022). ISG75 acts as an immunoglobulin Fc receptor and is the primary conduit for the uptake of the trypanocidal drug suramin, making it a vital target for both drug delivery and immune evasion strategies (Makarov et al., 2023; J Immunol, 2024). Despite their potential as therapeutic targets, their accessibility to drugs and antibodies is often restricted by the dense, protective VSG coat (Zoll et al., 2023).

Other names

ISG65ISG75Trypanosome invariant surface glycoproteinInvariant surface glycoprotein 65Invariant surface glycoprotein 75

Facilitates the cellular uptake of trypanocidal drugs like suramin via receptor-mediated endocytosis and inhibits host immune responses by binding complement components and immunoglobulins.