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dc.contributor.advisorUssher, James
dc.contributor.authorRoman, Tabatha
dc.date.available2018-11-14T00:34:39Z
dc.date.copyright2018
dc.identifier.citationRoman, T. (2018). MR1 surface expression on primary blood cells and their role in mucosal associated invariant T (MAIT) cell activation (Thesis, Bachelor of Biomedical Sciences with Honours). University of Otago. Retrieved from http://hdl.handle.net/10523/8587en
dc.identifier.urihttp://hdl.handle.net/10523/8587
dc.description.abstractMucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that bridge the innate and adaptive immune systems to provide rapid effector responses against a broad range of bacteria. MAIT cells are characterised by a semi-invariant Va7.2- Ja33/12/20 T cell receptor (TCR), which is restricted by the MHC-I-like molecule, MHC-related protein 1 (MR1). MR1, expressed on antigen presenting cells (APCs), binds and stabilises the MAIT cell activating ligand, an unstable pyrimidine, formed by the condensation of 5-amino-6-D-ribitylaminouracil (5-A-RU), an intermediate in riboflavin biosynthesis, with methylglyoxal (MG). Recognition of this MR1-presented ligand by MAIT cells results in TCR-mediated activation, which in turn results in the secretion of pro-inflammatory cytokines and cytotoxicity. Recent data generated using THP1 cells, a human monocytic cell line, as APCs, suggests that additional bacterially- derived signals also regulate MAIT cell activation. It is unknown whether these signals are also important in primary APCs. In this study, in vitro assays were performed to determine the regulation of MR1 surface expression on primary blood cells and the ability of primary blood cells to activate MAIT cells; a non-riboflavin-synthesising bacterial strain and synthetic MAIT cell activating ligand, 5-A-RU/MG, were used to separate the effects of different signals. The majority of primary blood cells showed enhanced MR1 surface expression in response to 5-A-RU/MG, but this was not enhanced by bacteria, except for CD14loCD16+ monocytes. While bacterial enhancement of MAIT cell activation in response to 5-A-RU/MG was also seen with primary APCs, it was dependent upon the presence of a CD8+ population in co-culture; the importance of this CD8+ population was also evident with THP1.hMR1 cells. In summary, this study has identified MR1 expression by a range of primary cells and a role for a CD8+ cell population in enhancing TCR-mediated MAIT cell activation by primary APCs in the presence of bacteria.
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectMAIT
dc.subjectcells
dc.subjectinnate-like
dc.subjectlymphocytes
dc.subjectimmunology
dc.subjectbacterial response
dc.subjectMR1
dc.subjectMucosal
dc.subject5-A-RU
dc.subjectblood
dc.subjectB cells
dc.subjectT cells
dc.subjectmonocytes
dc.subjectantigen presenting cells
dc.titleMR1 surface expression on primary blood cells and their role in mucosal associated invariant T (MAIT) cell activation
dc.typeThesis
dc.date.updated2018-11-13T23:39:06Z
dc.language.rfc3066en
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.nameBachelor of Biomedical Sciences with Honours
thesis.degree.grantorUniversity of Otago
thesis.degree.levelHonours
otago.interloanno
otago.openaccessAbstract Only
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