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My doctoral work in Immunology has been undertaken at the University of Western Australia (physically located at Royal Perth Hospital) and has focussed on one mechanism by which the human body determines self from non-self.  Natural Killer cells (a large granular lymphocyte - white blood cell) express the receptor KIR2DL4, which has been proposed to interact with the MHC ligand HLA-G. 


Killer Ig-like Receptor 2DL4 Does Not Mediate NK Cell IFN-γ Responses to Soluble HLA-G Preparations

Michael E. L. Le Page*,, Jodie P. Goodridge*,†‡, Elisabeth John*, Frank T. Christiansen* and Campbell S. Witt*,

The Journal of Immunology

Volume 192, Issue 2, pages xx-xx, January 2014


The MHC class Ib molecule HLA-G has previously been reported to be the ligand for the NK cell receptor killer Ig-like receptor (KIR)2DL4, but this remains controversial. In this study, we investigated IFN-γ production by freshly isolated NK cells in response to both soluble and solid-phase ligands, including anti-KIR2DL4 mAbs and rHLA-G. Although freshly isolated CD56bright NK cells produced IFN-γ in response to soluble HLA-G preparations, the response was found to be absolutely dependent on the presence of small numbers of contaminating CD56, CD14, CD11c+ myeloid dendritic cells (mDCs). HLA-G tetramers bound only to the contaminating mDCs in the NK preparations, and Abs to KIR2DL4 and HLA-G did not block NK cell IFN-γ production. NK cells did not respond to plate-bound HLA-G. Freshly isolated NK cells also produced IFN-γ in response to unpurified soluble anti-KIR2DL4 mAb but not to low endotoxin affinity–purified Ab. The data suggest that previous reports of functional interactions between KIR2DL4 and HLA-G may have resulted from the use of purified NK cells that were contaminated with mDCs and HLA-G preparations that were contaminated with material capable of stimulating mDCs to produce cytokines that stimulate NK cells to produce IFN-γ.

Genetic polymorphism of KIR2DL4 (CD158d), a putative NK cell receptor for HLA-G, does not influence susceptibility to asthma

M. E. L. Le Page1, J. P. Goodridge2, G. Zhang3, P. G. Holt4,5, P. Sly5, C. S. Witt1,6,*

Article first published online: 23 AUG 2013

Tissue Antigens

Volume 82, Issue 4, pages 276–279, October 2013


Human leukocyte antigen (HLA)-G is upregulated on the bronchial epithelium of asthma patients and genetic polymorphism affecting expression of HLA-G has been reported to influence susceptibility to asthma. As the NK cell receptor KIR2DL4 has been reported to induce interferon gamma (IFNγ) secretion when ligated with HLA-G, we postulated that the 9A/10A genetic polymorphism of KIR2DL4 which influences receptor structure may influence susceptibility to asthma. KIR2DL4 genotypes were determined in two cohorts of children (n = 219 and n = 1356) in whom total serum IgE, allergen-specific IgE, atopy, bronchial reactivity and asthma symptoms had been studied between birth and 14 years. No reproducible associations with KIR2DL4 genotype were identified, leading us to conclude that the KIR2DL4 9A/10A polymorphism has no influence on susceptibility to asthma.

My Science CV can be found here.

Some interesting asides resulting from the work:

Evolutionary tree for KIR2DL4 receptor in Primates:        PDF

Created: February 2012

Description: A quick demonstration of how to create a evolutionary tree (cladogram) using sequence alignments.

Confocal Microscopy of NK cell receptor KIR2DL4 and Choleratoxin:        PDF

Created:  July 2009

Description: We were able to replicate S. Rajagopalan et al’s finding that KIR2DL4 is present in endocytic vesicles, but could not show evidence of colocation with Choleratoxin, which would have been suggestive of a GPI-anchored form of KIR2DL4.