Killer cell immunoglobulin-like receptors (KIR) and reproductive success: the interaction between uterine NK cells and trophoblast HLA-C. (360G-Wellcome-079304_Z_06_Z)
Failure of trophoblast to invade and transform the uterine arteries during early pregnancy is associated with diseases such as pre-eclampsia and fetal growth restriction. However we do not know how trophoblast invasion is regulated. In a recent immunogenetic study, we showed that particular combinations of two polymorphic gene systems, Killer Immunoglobulin-like Receptors (KIR) in the mother and HLA-C2 in the fetus were associated with pre-eclampsia. The KIR are expressed by uterine Natural Kil ler (uNK) cells and their ligands are HLA-C molecules that are displayed by trophoblast. In this proposal we aim to define the biological and molecular mechanisms underlying this finding. We will use isolated primary uNK cells and placental trophoblast to define which activating and inhibitory KIR are expressed by uNK cells and what forms of HLA-C they recognise on trophoblast cells. A key goal is to determine how uNK cells respond when KIR on the uNK cells bind trophoblast expressing either HL A-C1 or HLA-C2 allotypes. By defining how NK responses to C1 and C2 allotypes differ we seek to understand the mechanism by which NK cells and trophoblast co-operate to establish a normal blood supply to the placenta and how this fails in pregnancies with particular KIR/HLA-C combinations.
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Grant Details
Amount Awarded | 285055 |
Applicant Surname | Moffett |
Approval Committee | Immunology and Infectious Disease Funding Committee |
Award Date | 2006-04-24T00:00:00+00:00 |
Financial Year | 2005/06 |
Grant Programme: Title | Project Grant |
Internal ID | 079304/Z/06/Z |
Lead Applicant | Prof Ashley Moffett |
Other Applicant(s) | Dr Andrew Sharkey |
Partnership Value | 285055 |
Planned Dates: End Date | 2009-09-30T00:00:00+00:00 |
Planned Dates: Start Date | 2006-07-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |