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Title: Impact of syndecan-4 on T cell-antigen presenting cell recognition and the immunological synapse
Author: Markiewicz, Anna Maria
ISNI:       0000 0004 2705 0745
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Syndecan-4 (SDC-4), a transmembrane heparan sulphate proteoglycan and a co-receptor of integrins for fibronectin, has been reported to modulate the adhesion of cells to a range of extracellular matrix ligands. In addition to the modulation of integrins, SDC-4 has been recently reported to modify the interaction of some growth factors with their receptors. T cells are essential effectors of the adaptive immune response. When conjugating with antigen-presenting cells (APCs), T cells transform their shape to enable formation of a specialised morphological structure, called the immunological synapse (IS). The IS formation is associated with the polarisation of signalling and adhesive molecules towards the APC. The IS is formed and stabilized by similar adhesive forces and structures as in the motile fibroblasts - an extensively studied model of syndecan function. In this thesis I have investigated the role of SDC-4 in T cell - APC recognition and the IS. First, I confirmed the tight regulation of SDC-4 expression in T cells during the process of activation. Flow cytometry and PCR data demonstrate increased presence of SDC-4 in stimulated human T cells compared to their resting counterparts, indicating involvement of SDC-4 in the processes of T cell activation. Transient transfection of exogenous SDC-4 into Jurkat T cells with low endogenous SDC-4 expression was used as a model to study the effect of increased SDC-4 expression on T cell function. Using live cell imaging and advanced data image analysis I have quantitatively demonstrated that SDC-4 transfected Jurkat T cells are less likely to modify their shape during IS formation when compared to mock transfected Jurkat T cells. I also observed a delay in T cell antigenic response caused by SDC-4 over-expression. Moreover, I was able to visualise the exogenous SDC-4 in the IS using confocal microscopy and demonstrate the independence of this phenomenon on T cell receptor. In summary, my observations indicate a regulatory role for SDC-4 in T cell adhesion causing delays in the IS formation and reduced transformation of T cell shape during conjugate formation.
Supervisor: Magee, Tony ; Seddon, John ; Law, Rob Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral