Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their
interaction with human leucocyte antigens (HLA). KIRs and HLA loci are highly polymorphic, and some of
their combinations have been found to protect against viral infections or to predispose to autoimmune disorders.
In particular, some activating KIRs profiles may be detrimental in autoimmune pathogenesis, and specific KIRs
may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control
of a given pathogen. So, considering that in the pathogenesis of many autoimmune disorders and infections innate
immunity plays a key role, the recent development for KIRs characterization, diseases monitoring, and treatment
becomes obvious. Here, we reviewed a growing body of evidence supporting the influence of KIRs variants and
their interaction with ligands in the development of the main human autoimmune and viral diseases, highlighting
the main applications in clinical practice.