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Investigating immune recognition of an epithelial stress antigen by Human gamma delta T cells AND Investigation into the chemokine profile of Ag-specific T cell responses in Multiple Myeloma and MGUS patients compared to age-matched controls.

Joyce, Stephen Paul (2012)
M.Res. thesis, University of Birmingham.

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Abstract

Project 1: The ‘lymphoid stress surveillance’ hypothesis proposes a role for γδ T cells in in the detection of epithelial stress. TCR mediated recognition of stress ligands by γδ T cells is currently poorly understood. This project aimed to characterise the molecular mechanisms of the interaction between of the Vδ1+ MAU γδ TCR with the ephrin receptor EphA2. EphA2 is a major target for anti-cancer treatments, and is upregulated on a range of epithelial tumours, a tissue enriched with Vδ1+ γδ T cells. We show that EphA2 activates MAU expressing JRT3.5 cells in a TCR dependant manner, by receptor downregulation and phosphorylation of key TCR proximal signalling proteins. It was also found that A-ephrins on the surface of the T cell are essential for the activation of JRT3 MAU by EphA2.

Project 2: Multiple Myeloma (MM) is an incurable haemopoietic malignancy, characterised by the accumulation of malignant plasma cells in the Bone Marrow (BM). MM cells express a group of proteins called Cancer Testis Antigens (CTA) whose expression is limited to the immune-privileged site of the testis in healthy adults. CTA specific CD8+ T cells in MM patients display poor in vivo effectiveness, and are poorly understood. Immuno dysregulation is a common occurrence in MM, with a dysregulation in the distribution and expression of key chemokines involved in lymphocyte trafficking such as CXCR3 and CXCR4, which may be a defensive mechanism by the tumour to protect against CTA specific T cells. This project aimed to characterise the chemokine receptor expression on CTA specific CD8+ T cells in MM patients, and it was discovered that MM patients have a reduction in CXCR3 and CXCR4 expression on CD8+ T cells in the blood, and that the chemokine receptor expression pattern of different viral specific CD8+ T cells are affected uniquely by MM.

Type of Work:M.Res. thesis.
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Cancer Studies
Subjects:RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Institution:University of Birmingham
ID Code:3467
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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