THEME 5 IMAGING PEPTIDE-MEDIATED IMMUNITY

“Mimicry”. Artwork depicting the way bacterial proteins mimic gluten proteins, causing an immune response to coeliac disease.
Dr Erica Tandori, artist in residence from the Rossjohn Laboratory at Monash University.

“We showed, at the molecular level, how receptors isolated from immune T cells from coeliac disease patients can
recognise protein fragments from certain bacteria that mimic those fragments from gluten.”

Within this theme, conceptual challenges lie in understanding how the T cell antigen receptor co-recognises peptide determinants while being presented by molecules encoded by the Major Histocompatibility Complex (MHC) – both in the context of protective immunity (e.g. to viruses) and aberrant immunity (eg autoimmunity). The Imaging CoE’s strategy is to develop reagents to characterise peptide-specific T-cells ex vivo and then use atomic and molecular imaging-based techniques to investigate the structural basis underpinning the interactions by the TCR.

PROF. JAIME ROSSJOHN

AT A GLANCE

Our work in 2019 has led to:
  1. An increased understanding of the mechanisms underpinning the immune response in Celiac disease (Dahal-Koirala et al. JBC, Mayassi et al. Cell)
  2. Unearthing a potential bacterially-driven environmental trigger in Celiac Disease (Petersen et al. NSMB).
  3. Suggesting molecular mimicry underpins an autoreactive response (Ooi et al, Nature Comms).
  4. Insights into TCR cross-reactivty and immune protection in influenza infection. (Koutsakos et al., Nature Immunol; Grant et al., Nature Comms; van de Sandt et al., Nature Comms).

 

ACTIVITY PLAN

  1. Continue to explore work on molecular basis underpinning impact of MHC on protective and aberrant immunity.

HIGHLIGHT

Bacterial link in coeliac disease

Bacterial exposure has been identified as a potential environmental risk factor in developing coeliac disease, a hereditary autoimmune-like condition that affects about one in 70 Australians.

It is estimated that half of all Australians are born with one of two genes that cause coeliac disease, and approximately one in 40 are likely to develop the condition. People with coeliac disease must follow a lifelong gluten-free diet, as even small amounts of gluten can cause health problems.

While environmental factors are known to trigger Coeliac Disease in those with the genetic predisposition, exactly how that works has remained unclear.

Scientists from the Monash Biomedicine Discovery Institute (BDI) and the Imaging CoE have now provided a molecular foundation for microbial exposure as a potential environmental factor in the development of coeliac disease.

The results of the study, done in collaboration with researchers at Leiden University Medical Centre and the Walter and Eliza Hall Institute of Medical Research, were published in the journal Nature Structural and Molecular Biology.

Co-Lead researcher Dr Hugh Reid, from Monash University, said the team showed, at the molecular level, how receptors isolated from immune T cells from coeliac disease patients can recognise protein fragments from certain bacteria that mimic those fragments from gluten.

Exposure to such bacterial proteins may be involved in the generation of aberrant recognition of gluten by these same T cells when susceptible individuals eat cereals containing gluten, he said.

“In coeliac disease you get aberrant reactivity to gluten and we have provided a proof-of-principle that there’s a link between gluten proteins and proteins that are found in some bacteria,” he said.

“That is, it’s possible that the immune system reacts to the bacterial proteins in a normal immune response and in so doing develops a reaction to gluten proteins because, to the immune system, they look indistinguishable – like a mimic.”

Dr Reid said the findings could eventually lead to diagnostic or therapeutic approaches to coeliac disease.

“Mimicry”. Artwork depicting the way bacterial proteins mimic gluten proteins, causing an immune response to coeliac disease.
Credit: Dr Erica Tandori, artist in residence, Rossjohn Laboratory at Monash University.

ACHIEVEMENT

Topping the highly cited researcher list for a second year in a row

Prof. Jamie Rossjohn, Chief Investigator to the Imaging CoE, has been ranked as a 2019 Highly Cited Researcher in the prestigious list released in November by Carivate Analytics.

The Monash Biomedicine Discovery Institute (BDI) researcher has been recognised for his exceptional research performance, determined by production of multiple highly cited papers that rank in the top one per cent by citations for a field and year.

Prof. Rossjohn’s research focus is on using structural biology to explain pre-T- cell receptor (TCR) self-association in T-cell development, and how the TCR specifically recognises polymorphic Human Leukocyte Antigen (HLA) molecules in the context of viral immunity and aberrant T- cell reactivity. He has unearthed structural mechanisms of HLA polymorphism impacting on drug and food hypersensitivities, as well as Natural Killer cell receptor recognition. He has pioneered molecular understanding of lipid-based immunity by T cells, revealing that it can differ fundamentally from peptide-mediated adaptive immunity.

Prof. John Carroll, Director of the Monash BDI, congratulated him on his achievement.

“By making the Highly Cited Researcher list two years running, Jamie has demonstrated his continued leadership in the field of immunology,” Professor Carroll said.

The Highly Cited Researcher list, now in its sixth year, determines the ‘who’s who’ of influential researchers, drawing on data and analysis to identify the world’s leading researchers who have demonstrated significant and broad influence.

Article Source:
Monash University, Monash Biomedicine Discovery Institute