Congratulations to Australian Synchrotron scientist Nathan Cowieson, who is co-author of a paper just published in Nature, along with colleagues at Monash University.

Nature is arguably the world’s most prestigious and widely read scientific journal. It is also considered to be one of the most highly cited interdisciplinary science journals of its kind.

In simple terms, the work revealed details of the ‘quality control’ process that immature T cells, a kind of white blood cell that plays an important part in the body’s immune system, must undergo before they can mature. The ‘T’ in T cell stands for thymus, which is where the T cells mature.

The study (Nature 467: 844-8, 14 October 2010) from Jamie Rossjohn’s laboratory at Monash University describes the underlying molecular mechanism of T cell selection and maturation. A breakthrough in the field of cellular immunity, the finding relied on the Australian Synchrotron’s protein crystallography and small-angle x-ray scattering beamlines. Nathan collaborated with Jamie Rossjohn’s research group while working at Monash University in Matthew Wilce’s laboratory before joining the Australian Synchrotron in 2009.

T cells are a population of cells that play a key role in cell-mediated immunity. On the surface of each T cell is a T cell receptor (TCR) composed of two polypeptide chains that bind together when an antigen is present leading to T cell activation and an immune response. Random recombination or shuffling within the TCR genes gives rise to variations in the receptor from T cell to T cell that allows populations of T cells to recognise a wide range of pathogenic organisms.

While gene shuffling and variation are key features of the TCR the process also inevitably gives rise to variations that are no longer able to perform the dimerisation and signalling functions of the TCR. For this reason T cells go through a quality checkpoint during their maturation. In this process an invariant pre-T cell TCR chain binds to the variant T cell receptor chains in the absence of an antigen and in this context the binding and signalling allow the immature cells to become mature T cells.

The Nature paper describes the atomic resolution structure of a pre-T cell dimeric complex solved by protein x-ray crystallography at the macromolecular crystallography beamlines at the Australian Synchrotron. The structure reveals the molecular mechanism by which these proteins dimerise and how the pre-T cell chain 'samples' the variant chain to test for integrity. The mode of dimerisation seen in the crystal structure is validated in solution by experiments conducted at the small angle x-ray scattering (SAXS) beamline at the Australian Synchrotron.

Click here to read the paper, entitled ‘The structural basis for autonomous dimerisation of the pre-T-cell antigen receptor’, as an abstract or in full.

Nathan said he was “privileged to play a small part in this research and felt strongly that science like this reflected the hard work of both users and staff”.

“The work described in the Nature paper could not have happened without significant input from other scientists, including the work of major contributor and PhD student Siew Siew Pang, and the important work of Nicole La Gruta, Zhenjun Chen and Matthew Wilce on the MX and SAXS beamlines,” Nathan said. He noted the contribution of Professor Jamie Rossjohn, who heads the laboratory where much of the work was done.

“The research described in this paper is also a real testament to the great instrument that the synchrotron is.”