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Title: MHC molecules of human trophoblast
Author: Apps, R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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The maternal decidua and the fetally-derived placenta are specialised tissues which have been developed to support mammalian reproduction. Unusual features of the decidua include a leukocyte population dominated by 70% CD56 bright NK cells. Invasive placental trophoblast cells penetrate the decidua and express a unique repertoire of Major Histocompatibility Complex (MHC) molecules, which are likely to be significant in maternal immune recognition. Human trophoblast cells do not express the classical HLA-A and HLA-B molecules that are ligands for T cells, but do express HLA-C molecules which are the dominant ligand for NK cells, as well as the non-classical HLA-E and HLA-G molecules. HLA-G is particularly interesting as it is expressed by no other tissues and has no known function. I first investigated expression of the MHC-related ULBP and MIC molecules at the human implantation site, but found no evidence for expression of their protein. I then characterised the conformation of HLA-C and HLA-G molecules at the surface of normal human trophoblast cells isolated from the first trimester of pregnancy at the time of placentation. The majority of HLA-C molecules on trophoblast cells were present in a conventional, b2m-dissociated open conformers were detected at the cell surface. This suggests that trophoblast HLA-C molecules will provide efficient ligands for KIR receptors on maternal NK cells. In contrast, a significant proportion of HLA-G molecules were found to exist in a disulphide-linked homodimeric complex. This complex was a homodimer of two conventional b2m-dissociated HLA-1 molecules, which is a conformation unique to HLA-G. Dimeric HLA-G complexes on trophoblast showed substantially higher affinity for the LILRB1 receptor which was expressed by all decidual antigen-presenting cells. This may represent a trophoblast-specific signal to the local maternal uterine immune system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available