NATURAL KILLER CELLS
Dr Clair M. Gardiner
Dr. Clair M Gardiner
Phone: +353-1-896-1614
Fax: +353-1-677-2400
E-mail: clair.gardiner@tcd.ie
Location: Room 4.31, Biomedical Sciences Institute |
|
Research Interests
Natural Killer (NK) cells are important effector cells in the immune system where they act as a bridge between the innate and acquired immune responses. Their primary function described to date has been their ability to kill virally infected and cancer cells. In the last ten years, numerous surface receptors have been discovered which play a fundamental role in how NK cells recognize their targets. Two main families of receptors for HLA class I have been discovered on human NK cells: Killer cell Immunoglobulin-like receptors (KIR) and CD94/NKG2 heterodimers. The KIR receptors are an extremely diverse family of receptors. In addition to receptors for HLA, NK cells also express pattern recognition receptors e.g. TLRs and Nod proteins. We are also investigating how these function on NK cells in terms of pathogen recognition.
Role of Receptor Diversity in NK cell Function
Intragenic diversity exists within KIR genes. We recently reported that two KIR genes, KIR3DL1 and KIR3DL2 were highly polymorphic. We are currently involved in investigating functional consequences of this diversity. In particular, we are looking at how diversity of KIR3DL1 influences its ability to recognize target cells. Indeed, we have found that alleles of KIR3DL1 differ in their ability to recognise HLA class I antigen. This has important implications for how NK cells recognize down-regulated or altered HLA expression during viral infections.
Genetics of NK cell receptors
KIR receptor genetics are complex. The factors which control expression of KIR genes are poorly understood and phenotypes vary dramatically. In collaboration with Prof. Derek Middleton’s group in City Hospital, Belfast, we are characterising KIR diversity in the Irish population. In addition, we are investigating the contribution of genotype to phenotypic expression of these genes.
Role of NK cell receptors in disease populations
Given that DNA polymorphisms are increasingly associated with disease and that KIR genes are highly polymorphic, we predict disease associations especially where NK cells play a functionally important role or where NK cell receptor genome regions (chromosomes 19q13.4 and 12p13.1) have already been implicated in the disease. One study in our lab is investigating the role of KIR genotype and phenotype in disease outcome in HCV infection. This project is in collaboration with the Irish Hepatitis C Virus Research Consortium.
Pattern recognition receptors and human NK cells
Toll-like Receptors
We have recently shown that human NK cells express most of the TLRs. In particular, we have been working on TLR3, TLR7 and TLR8 and characterising their expression and function on NK cells. We have shown that all play a role in activating NK cells and that accessory cells are important, particularly in the TLR7/8 pathway, for cytokine production.
NOD proteins
Similar to TLRs, NOD proteins recognise pathogen associated molecular patterns. We are investigating expression and function of different NOD proteins in human NK cells.
Research Personnel
Dr. Megan Dring
Dr. Kiva Brennan
Dr. Ciara Keane
Maria Morrison
Sinead Dunphy
Louise Quinn
Financial Support
Science Foundation Ireland
Health Research Board
The National Children's Research Centre, Our lady's Children's Hopsital, Crumlin, Dublin 12
Recent Publications by Natural Killer Cells Group
[Top of Page] |
