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Title: Characterisation of the immunomodulatory receptors ILT-1 and ILT-3
Author: Brown, D.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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Dendritic cells (DC) bridge the innate and adaptive immune responses by recognising foreign antigens with non-rearranging receptors and then displaying these antigenic materials to cells of the acquired immune system. Expression of ILTs, a family of immunoregulatory receptors, is believed to influence the antigen presenting functions of DC. The work in this thesis set out to explore the relationship between the activating ILT-1 receptor, inhibitory ILT-3 receptor and myelomonocytic cells, including DC and macrophages. Examination of the cellular distribution of ILT-1 and ILT-3 revealed expression on the majority of myeloid cell types. The predominant expression was found on myelomonocytic cells. The level of ILT-1 and ILT-3 expression by DC, macrophages and monocytes was altered by exposure of these cells to inflammatory and anti-inflammatory stimuli. TNF-α and PGE2, known pro-inflammatory agents, decreased the expression of ILT-1 and ILT-3. The impact of ILT-1 and ILT-3 antibody cross-linking on myelomonocytic cell phenotype, mRNA and cytokine profiles was examined. ILT mediated activation of DC altered the expression of cell surface proteins important for the stimulation of CD4+ T cells. However, when changes in mRNA expression were examined by microarray, ILT receptors apparently had little effect, suggesting that they exert their effects principally at the post-transcriptional level. Using ILT-1 and ILT-3 Fc fusion proteins, a candidate-screening approach was adopted to identify their ligands. Neither ILT-1 nor ILT-3 bound MHC Class I molecules. ILT-1 Fc bound to cultured CD8+ T cells, implying the existence of an activation-induced ligand on a CD8+ T cell subset that is not a classical MHC molecule. In conclusion, my work supports the hypothesis that ILT-1 and ILT-3 regulate the maturational state of myelomonocytic antigen presenting cells and, thereby, influences the nature of T cell responses.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available