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You searched for +publisher:"University of New South Wales" +contributor:("Grewal, Thomas, University of Sydney"). One record found.

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University of New South Wales

1. Cornely, Rhea. The role of Annexin A6 in T cell activation.

Degree: Centre for Vascular Research, 2013, University of New South Wales

The activation of T cells by an antigen presenting cell is one of the essential first steps for an effective immune response. Activation of the T cell receptor (TCR) leads to fundamental changes to T cell morphology, cytoskeletal rearrangement, membrane order and the formation of TCR microclusters which then propagate downstream signalling. TCR signalling eventually induces T cell proliferation as well as the production and secretion of interleukin 2 (IL-2) which binds to the IL-2 receptor and further stimulates T cell proliferation in an autocrine and paracrine fashion. Both signalling processes are dependent on specialised membrane domains enriched in cholesterol also termed lipid rafts and were found to sustain transient interactions with the cortical actin meshwork.Annexin A6 (AnxA6) is a calcium-activated cytosolic phospholipid membrane binding protein which has been suspected to play a role in T cell development and is upregulated in a wide range of immune cells including T cells. AnxA6 is involved in receptor endocytosis, vesicle budding and cholesterol homeostasis. It has been found to preferentially bind cholesterol-rich phospholipid membranes and to interact with the cortical cytoskeleton to allow endocytosis and vesicle budding.The aim of this study was to show that AnxA6 is crucial for an effective T cell mediated immune response. It was hypothesised that AnxA6 influences receptor signalling directly by mediating a link between the cortical cytoskeleton and cholesterol-rich membrane domains and thus AnxA6 might be part of a mechanism to target receptors to a specific membrane environment. Alternatively, AnxA6 influences signalling processes indirectly through maintaining the optimal composition of the plasma membrane due to its involvement in cholesterol homeostasis – as AnxA6 plays a role in cholesterol transport from intracellular membranes to the plasma membrane as well as low-density lipoprotein endocytosis.In this study a delayed-type contact hypersensitivity was elicited in AnxA6 knock-out mice to generate a T cell mediated immune response in vivo. The results showed that AnxA6mice did mount a T cell mediated immune response but the levels of proliferating CD4+ T cells were significantly lower than in wild type mice.Investigating the source of this proliferation defect, western blot, fluorescence microscopy, qPCR and flow cytometry approaches were used to measure the response of primary murine T cells to T cell receptor as well as IL-2 receptor stimulation. Neither the early nor the late response of TCR signalling was affected in AnxA6-/- T cells. Instead, activated AnxA6-/- T cells secreted more IL-2 and the response to IL-2 stimulation was found to be impaired in AnxA6-/- T cells.In parallel, it was investigated if and how the membrane composition of primary AnxA6-/- T cells was different from wild type T cells. The membrane order of TCR stimulated as well as naïve cells was measured with polarity-sensitive dye Laurdan. To characterise the cholesterol content and phospho- and sphingolipid… Advisors/Committee Members: Gaus, Katharina, Centre for Vascular Research, Faculty of Medicine, UNSW, Grewal, Thomas, University of Sydney.

Subjects/Keywords: IL-2 receptor; T cell activation; TCR; Membrane lipids

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APA (6th Edition):

Cornely, R. (2013). The role of Annexin A6 in T cell activation. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/53646 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12341/SOURCE02?view=true

Chicago Manual of Style (16th Edition):

Cornely, Rhea. “The role of Annexin A6 in T cell activation.” 2013. Doctoral Dissertation, University of New South Wales. Accessed October 31, 2020. http://handle.unsw.edu.au/1959.4/53646 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12341/SOURCE02?view=true.

MLA Handbook (7th Edition):

Cornely, Rhea. “The role of Annexin A6 in T cell activation.” 2013. Web. 31 Oct 2020.

Vancouver:

Cornely R. The role of Annexin A6 in T cell activation. [Internet] [Doctoral dissertation]. University of New South Wales; 2013. [cited 2020 Oct 31]. Available from: http://handle.unsw.edu.au/1959.4/53646 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12341/SOURCE02?view=true.

Council of Science Editors:

Cornely R. The role of Annexin A6 in T cell activation. [Doctoral Dissertation]. University of New South Wales; 2013. Available from: http://handle.unsw.edu.au/1959.4/53646 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12341/SOURCE02?view=true

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