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Title: Killer cell immunoglobulin-like receptor (KIR) and T cell phenotype
Author: Salam, Arafa
Awarding Body: St George's, University of London
Current Institution: St George's, University of London
Date of Award: 2018
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Killer cell immunoglobulin-like Receptors (KIR) represent a highly polymorphic family of activating and inhibitory receptors, which bind to HLA. KIR are predominantly found on NK cells but evidence suggests that KIR expression on T cells may critically modulate cellular responses. This project set out to explore the link between inhibitory KIR genotype/phenotype, T cell homeostasis and viral infection. Using multi-colour flow cytometry, the impact of KIR genotype on immunosenescence was first investigated in 70 healthy elderly subjects. The number of KIR genes did not influence the accumulation of TEMRA in T cell subpopulations but was positively associated with CD57 expression in transitional memory (CD4+ and CD8+) and TEMRA (CD4+) T cells when controlled for age and CMV-seropositivity. The presence of the specific HLA ligand for KIR was associated with increased CD57 expression in more differentiated cells. Secondly, the impact of differentiation on KIR expression was tested for three inhibitory KIR (KIR2DL1, KIR2DL2/3 and KIR3DL1). All three receptors showed a similar pattern: KIR expression occurred earlier in differentiation in CD4+ than CD8+ T cells and was increased in hepatitis C infected subjects (n=15). Furthermore, KIR expression was strongly associated with markers of proliferation (Ki-67) and apoptosis (Annexin V), but not survival (Bcl-2) in healthy controls (n=15) and Hepatitis C infected subjects (n=15). Reanalysis by subject genotype did not identify specific KIR-HLA interactions, although numbers were small. Finally, analysing KIR expression on virus-specific CD8+ T cells in subjects with chronic virus infection (HIV, n=15; HTLV-1, n=9) demonstrated that virus-specific CD8+ T cells appeared to express elevated levels of KIR expression. These findings suggest that KIR plays a pivotal role in CD4+ and CD8+ T cell homeostasis and specifically in CD8+ anti-viral responses.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available