Multiple mechanisms underlie the tolerance shown by the maternal immune system; one of these involves the selective expression of cell surface Human Leukocyte Antigen (HLA) receptors. HLA receptor biosynthesis and display requires multiple intracellular mechanisms including interaction with the cytoskeleton. Previous studies on somatic cells other than trophoblasts have shown that HLA receptor distribution is linked to the cytoskeleton. It is postulated that the cytoskeleton is responsible for the structural integrity of the cell, specifically in implantation, as the extra-villous trophoblast (EVT) cytoskeletal proteins are essential for endometrium invasion and cell adhesion. To gain an understanding of the role of the cytoskeleton on feto-maternal interactions the trophoblast cytoskeleton in relation to HLA was examined. All trans retinoic acid (A TRA) and Cytochalasin D (Cyto D), both known to alter the cytoskeleton were studied on the established EVT model cells JEG-3, and ACH-3P. The presence, expression pattern and topographical distribution of the HLA receptors and cytoskdetal proteins on both cell lines were studied using advanced bioimaging techniques. These in vitro studies confirm previous knowledge suggesting a highly selective pattern of HLA class I antigens and suggest interaction between loci products known as HLA-C and HLA-G. The cytoskeleton products actin, talin and integrins were also detected in both the trophoblast cell lines. Qualitative and quantitative co-localisation studies with confocal microscopy suggest interaction between HLA-G and actin filaments. The effect of ATRA and Cyto D followed a similar trend in all the proteins of interest (HLA-G, actin filaments, talin and integrins) indicating that these three proteins form a single a single oligomeric and functional structure. This study favors the hypothesis that interactions between HLA molecules and cytoskeleton structures contribute to tolerogenic mechanisms operating during human pregnancy development.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:654467 |
| Date | January 2014 |
| Creators | Jain, Pallavi |
| Publisher | University of Essex |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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