MRC DTA Studentship: Paternal antigens, maternal killer lymphocytes and reproduction

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The mother's immune system senses her developing child as if it was a foreign body, since the child expresses paternal genes. But why do the mother's lymphocytes not attack and destroy the child? One current hypothesis is that Nature has negotiated this apparent immunological paradox by actually taking advantage of the parental genetic disparity to exploit the mother's attack against the father's genes. The prediction of this hypothesis is that paternal antigens (Major Histocompatibility Complex, MHC) and maternal lymphocyte receptors (Killer cell Immunoglobulin-Like receptors, KIR) are essential determinants of the feto-maternal unit. Recent evidence that certain MHC-KIR combinations correlate with lower risk of preeclampsia and higher reproductive success support this hypothesis (Hiby, J Exp Med, 200:957). Preeclampsia is a serious complication of pregnancy, whereby the foetus does not receive sufficient blood supply from the placenta and the mother is ill with high blood pressure. Maternal uterine Natural Killer (uNK) lymphocytes are thought to mediate immunological recognition of paternal antigens. By making inflammatory and angiogenic factors, which remodel placental haemodynamics, uNK cells may contribute to crucial events towards securing vital blood supply and preventing preeclampsia (Paraham, J Exp Med, 200:951). The mechanisms leading to these beneficial interactions are not fully understood. We are developing a new model system to dissect out these mechanisms.

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