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Title: Functional roles of the leukocyte immunoglobulin-like receptors in infectious disease
Author: Hudson, Laura
ISNI:       0000 0004 7427 1268
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2018
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The Leukocyte Immunoglobulin-Like Receptors (LILR) are a family of innate immune receptors expressed on myelomonocytes and selected lymphocytes, and able to influence the course of innate and adaptive immunity. Group 1 LILR bind MHC-I molecules, and allelic variations between MHC-I alleles with resulting differences in binding affinity to LILR may influence the outcomes of various immune-pathologies and infections. This project determined the expression and function of individual LILR on innate and adaptive immune cells, as well as assessing the potential relevance of specific receptors in viral infection with HIV-1. Flow cytometric analyses were used to determine expression of LILRB1, LILRB2 and LILRA2 on lymphocyte subsets and monocytes. LILRB1 expression was identified on T-cell subsets and B-cells where expression was seen on the memory B-cell subset in particular. LILRB1 expression on memory B cells increased following TLR7/8 and 9 activation, indicating a potential role for the receptor as a regulator of memory reactivation and terminal differentiation. The percentage expression of LILRB2 in Monocytes was constitutively greater than that of LILRB1 and LILRA2. Following TLR activation on monocytes, LILRB1 levels increased dramatically, whilst LILRA2 levels decreased. In functional assays, LILRB1 cross-linking appeared to inhibit IL-6 secretion from both B cells and monocytes, whilst enhancing phagocytosis in monocytes. Studies using panels of LILR transfectants and Fc fusion proteins did not identify any receptors capable of direct binding to HIV-1, or the associated glycoprotein, gpl20. Findings from this project support a role for LILR in the response to viral infection, identifying new immune cell subsets and mechanisms that may be regulated by LILR. The potential for personalised treatment regimens targeting these receptors is an exciting future prospect.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available