AUTHOR=Kӧrner Christian , Altfeld Marcus 

TITLE=Role of KIR3DS1 in human diseases

JOURNAL=Frontiers in Immunology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2012.00326

DOI=10.3389/fimmu.2012.00326

ISSN=1664-3224

ABSTRACT=<p>The function of natural killer (NK) cells is controlled by several activating and inhibitory receptors, including the family of killer-immunoglobulin-like receptors (KIRs). One distinctive feature of KIRs is the extensive number of various haplotypes generated by the gene content within the <italic>KIR</italic> gene locus as well as by highly polymorphic members of the KIR gene family, namely <italic>KIR3DL1/S1</italic>. Within the <italic>KIR3DL1/S1</italic> gene locus, <italic>KIR3DS1</italic> represents a conserved allelic variant and displays other unique features in comparison to the highly polymorphic <italic>KIR3DL1</italic> allele. <italic>KIR3DS1</italic> is present in all human populations and belongs to the <italic>KIR</italic> haplotype group <italic>B</italic>. <italic>KIR3DS1</italic> encodes for an activating receptor featuring the characteristic short cytoplasmic tail and a positively charged residue within the transmembrane domain, which allows recruitment of the ITAM-bearing adaptor molecule DAP12. Although HLA class I molecules are thought to represent natural KIR ligands, and HLA-Bw4 molecules serve as ligands for KIR3DL1, the ligand for KIR3DS1 still needs to be identified. Despite the lack of formal evidence for an interaction of KIR3DS1 with HLA-Bw4-I80 or any other HLA class I subtype to date, a growing number of associations between the presence of <italic>KIR3DS1</italic> and the outcome of viral infections have been described. Especially, the potential protective role of <italic>KIR3DS1</italic> in combination with <italic>HLA-Bw4-I80</italic> in the context of HIV-1 infection has been studied intensively. In addition, a number of recent studies have associated the presence or absence of <italic>KIR3DS1</italic> with the occurrence and outcome of some malignancies, autoimmune diseases, and graft-versus-host disease (GVHD). In this review, we summarize the present knowledge regarding the characteristics of KIRD3S1 and discuss its role in various human diseases.</p>