Clone REA168 recognizes the CD158e1/e2 antigens, which are single-pass type I membrane proteins. CD158e is expressed on CD56dim
natural killer (NK) cells and CD8+
T cells. Killer cell immunoglobulin-like receptors (KIRs) contribute to the regulation of NK cell–mediated cytotoxicity. The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long or short cytoplasmic domain. According to the length of their cytoplasmic tail, KIRs can be further subdivided into inhibitory KIRs and activating KIRs. The CD158e1 antigen is also known as KIR3DL1 (KIR, three Ig like domain extracellular domains, long cytoplasmic tail, 1) and the CD158e2 antigen as KIR3DS1 (KIR, three extracellular Ig like domains, short cytoplasmic tail, 1). Within the KIR3DL1/S1 gene locus, CD158e2 represents a conserved allelic variant and displays unique features in comparison to the highly polymorphic CD158e1 allele. CD158e1 provides an inhibitory signal of NK cell lytic activity upon interaction with its specific ligand, HLA-Bw4. Despite the lack of formal evidence for an interaction of CD158e2 with HLA-Bw4 or any other HLA class I subtype, a growing number of associations between the presence of CD158e2 and the outcome of viral infections have been described. Especially, the potential protective role of CD158e2 in combination with HLA-Bw4-I80 in the context of HIV-1 infection has been studied intensively.