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Published Back-to-back First Authors Papers

Clarke and Kwok





On 3rd March, two PhD students from the Rossjohn Lab, Andrew Clarke and Kwok Wun, published back-to-back 1st author papers in Immunity. Andrew and Wun were invited to discuss their findings and comment on their perception of the importance of getting a high impact paper for their PhD.

Andrew Clarke
My paper, "A Molecular Basis for NKT Cell Recognition of CD1d-Self-Antigen", provides the first insights into the molecular mechanisms governing how Natural Killer T-cells recognise self-antigens. Briefly, a conserved mechanism between foreign and ‘self' antigens was observed. This work provides groundwork for a number of diseases including cancer, ischemia-reperfusion injury, sickle cell disease and innate responses to infection.
In a competitive field such as Immunology, it is important to make a name for yourself as a researcher. Being first-author in a high impact journal will help raise my profile in the field, and hopefully put me ahead of the pack when applying for funding and fellowships once I have completed my PhD.

Mallevaey, T., Clarke, A.J., et al. Immunity March 3rd 2011 "A Molecular Basis for NKT Cell Recognition of CD1d-Self-Antigen".

Kwok Wun
The semi-invariant Natural Killer T (NKT) cells are implicated in several immune responses such as tumour surveillance, inflammation and autoimmunity. Unlike conventional T cells that recognise peptide antigens when presented by the MHC, NKT cells recognise glycolipids such as alpha-GalCer that when presented by a MHC class I like molecule, CD1d, invoke a potent immune response.

In the publication, we had utilised a combination of biophysical techniques such as Surface Plasmon Resonance (SPR), X-ray crystallography as well as cell-based assays to gain a greater understanding of how the NKT T cell receptor (NKT TCR) recognises and differentiates between different closely related alpha-GalCer analogues presented by CD1d. This project is a continuation of the highly successful research involving the NKT TCR-CD1d-alpha-GalCer interaction that was previously published through the collaboration formed between the Rossjohn and McCluskey & Godfrey labs in Melbourne University (Borg, NA, et al. 2007. Nature and Pellicci, DG, Patel, O, Kjer-Nielsen, L. et al. 2009. Immunity).

In summary, through the use of these closely related alpha-GalCer analogues, we have determined a molecular basis for the fine specificity of CD1d-restricted antigens and functional responses by the NKT cells. Despite the structural differences within these analogues, the NKT TCR maintains a similar docking mode in recognising CD1d presenting these analogues. It was subsequently identified that modifications on certain regions of the alpha-GalCer antigen impacted NKT cell proliferation or cytokine production either directly through the differences in binding affinity of the NKT TCR-CD1d-analogues or indirectly through an altered antigen processing pathway within the cells. Furthermore, we have also determined that the potency of an alpha-GalCer analogue is controlled by the half-life of the NKT TCR-CD1d-analoge interaction.

There is a saying that publications are the universal currency in the scientific world. As such, I feel extremely fortunate to have my PhD research published in such a high impact paper. It is indeed very satisfying to see the effort I have put into the project eventuate into a publication. It certainly makes all those extra hours spent in the laboratory during the weekends seemed worthwhile and is just a small price to pay.

Wun, KS., Cameron, G., et al. Immunity March 3rd 2011 "A Molecular Basis for the Exquisite CD1d-Restricted Antigen Specificity and Functional Responses of Natural Killer T Cells"

Andrew and Wun acknowledged that none of this research would have been published without the help of their collaborators, Garth Cameron (Co-first author from the Godfrey's Lab) and Thierry Mallevaey (Co-first author, Gapin lab).

Both Andrew and Wun would like to take this opportunity to thank all the co-authors and their supervisors for their guidance and help in this project.