Cluster of differentiation 81, CD81, also known as Tetraspanin-28, Tspan28, and target of the antiproliferative antibody 1, TAPA-1, is a transmembrane (TM) protein, member of the tetraspanin family, and plays a role in intercellular interactions and cellular trafficking.¹

CD81 is composed of 236 amino acids, four TM regions, intracellular N- and C-termini, small (EC1) and large (EC2) extracellular loops, a short intracellular loop between TM2 and TM3, and is characterized by a bound cholesterol molecule in an intramembrane pocket between the two pairs of TM helices capped by the EC2 domain. The binding of cholesterol alters the conformation of the protein, a process which is exploited by certain viruses to enter cells. CD81 serves as a co-receptor for several viruses, including hepatitis C (HCV), human immunodeficiency virus type 1 (HIV-1), herpes simplex virus 1 (HSV-1), influenza A (IAV), and Chikungunya, as well as certain bacteria and parasites. CD81 can interact with other TM proteins to form clusters and higher-order protein complexes.^1,2

CD81 is highly conserved in mammals, expressed on all primary B-lineage cells from early B-cell development stages, and associates with CD19 on the cell surface. CD81 engagement on mature human B-cells induces an antiproliferative effect.³

CD81 is involved in neurotransmission, cell signaling, cell proliferation, and protein trafficking, as well as the immune, reproductive, genitourinary, and auditory systems. CD81 is also implicated in oncology, viral infection, and inflammation.^1,2