Role of a KIR/HLA-C allorecognition system in pregnancy

Abstract

Decidual natural killer (NK) cells are thought to play a significant role in the allorecognition mechanisms during pregnancy. Through their activating and inhibitory receptors they may recognize selectively class I HLA alleles expressed on invading trophoblast and provide self-signals to control NK responses, thus regulating the maternal immune response at the fetomatenal interface. Killer immunoglobulin-like receptors (KIR) constitute one of the families of class I MHC receptors which are expressed on NK cells. Their repertoire includes both activating and inhibitory receptors, most of which recognize specific epitopes on HLA-C molecules and can either activate NK cell responses or abort activating signals and inhibit NK cell functions. Since KIRs are expressed on decidual NK cells and the HLA-C molecules that they recognize are also expressed on invading trophoblast, KIR receptors may play a regulatory role in pregnancy by interacting with their trophoblastic HLA-C counterparts and providing trophoblast damage evading signals (KIR/HLA-C allorecognition system). Our hypothesis that the KIR/HLA-C system might be ineffective in some unsuccessful pregnancies, has been investigated in women with unexplained spontaneous abortions. Our results suggest that a limited maternal repertoire of inhibiting KIRs (inhKIRs) and/or lack of maternal inhKIR-fetal HLA-C epitope matching may predispose to miscarriage.