Uncovering how T cells recognise the SARS-CoV-2 virus spike protein

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The immune system is vitally important for resolving COVID-19 when individuals are infected with the SARS-CoV-2 virus. Moreover, the vaccines that are being administered to millions of people across the globe are designed to ‘pre-warn and arm’ the immune system so that if infected with SARS-CoV-2, individuals are significantly less likely to develop severe disease or die.  Here, two crucial arms of the immune system, namely B cells and T cells, play a central role.

While we have a molecular understanding of how antibodies, which are produced by B cells, can bind and neutralise the spike protein from SARS-CoV-2, up until now researchers did not know how T cell receptors (TCRs), which are found on T cells, recognise antigens that arise from the spike protein.

“T cells play an important role in immunity against both SARS-CoV-2 vaccination and severe acute respiratory infection. Although T cells in COVID-19 have been studied previously, the molecular basis underpinning TCR recognition of SARS-CoV-2 remained unknown. It has been a pleasure working with the Monash University team to conduct this extremely important work to understand how T cells recognise an antigen from SARS-CoV-2,” said University of Melbourne Professor Katherine Kedzierska, a laboratory head at the Peter Doherty Institute for Infection and Immunity.

In a world first finding, co-led by Monash University’s Dr Priyanka Chaurasia, Dr Jan Petersen and Professor Jamie Rossjohn, and Professor Kedzierska, the team analysed the TCR recognition of a spike protein fragment when presented by an immune molecule, termed Human Leukocyte Antigen A2 (HLA-A2). This work, which utilised the Australian Synchrotron, was published in the Journal of Biological Chemistry. 

“This is a piece of a larger puzzle. While SARS-CoV-2 continues to evolve, we have to build our understanding of how effective immune responses work,” said Dr Jan Petersen.

The team provided important molecular insight into understanding how T cells of the human immune system respond to SARS-CoV-2. Different individuals mount differing immune responses to SARS-CoV-2, and this work provided fundamental insight into such an immune response.

Read the publication in the Journal of Biological Chemistry titled Structural basis of biased T cell receptor recognition of an immunodominant HLA-A2 epitope of the SARS-CoV-2 spike protein

[Paper: J Biol Chem. 2021 Aug 10;297(3):101065. doi: 10.1016/j.jbc.2021.101065.]

Original article

Also featured in ANSTO article: Understanding how adaptive immune cells recognise and interact with the SARS CoV-2 virus

Over $43m awarded to Monash researchers in latest round of NHMRC Investigator Grants

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Monash University has been awarded more than $43 million in National Health and Medical Research Council Investigator Grants, and a new Centre for Research Excellence, to support the work of more than 30 research leaders.

Better treatments for autoimmune kidney disease and vasculitis, better understanding of the progression of Alzheimer’s disease, improving the efficacy of clinical trials for surgical patients and T cell research are among the projects to receive funding.

The NHMRC also announced a new $2.5 million Centre for Research Excellence to transform outcomes of critically ill patients in ICU (CRE-ICU), to be led by Professor Carol Hodgson from the School of Health and Preventive Medicine and Deputy Director of the Australian and New Zealand Intensive Care-Research Centre.

The grants are part of $471.9 million in health and medical research grants announced by Federal Health Minister Greg Hunt. The funding will support hundreds of research leaders and teams around the country to undertake research that will ultimately save lives and make Australians healthier.

Investigator Grants support researchers at any stage of their careers, allowing researchers the flexibility to innovate by taking their research in new directions and forming collaborations.

The grants are focused on the four pillars of health and medical research: biomedical, clinical, public health and health services.

Monash University President and Vice-Chancellor Professor Margaret Gardner AC said the projects to receive funding demonstrate the scale and diversity of Monash research, and the important work being done to support health and medical innovations.

“I am delighted that 31 Monash researchers will share in this significant amount of NHMRC funding, and I congratulate and thank them for the crucial work they are doing to improve the health and wellbeing of our communities,” Professor Gardner said.

“The flexibility and collaboration that this investment allows, as well as the establishment of a new Centre for Research Excellence in ICU, will enable our researchers to explore creative solutions to some of the greatest health challenges we face today.”

Complete list of recipient projects:

‘A molecular investigation into T cell antigen receptor function and dysfunction in humans’

Professor Jamie Rossjohn

Faculty of Medicine, Nursing & Health Sciences

Awarded:$3,927,015 (Leadership 3)

‘Improving the Impact and Efficiency of Perioperative Clinical Trials’

Professor Paul Myles

Faculty of Medicine, Nursing & Health Sciences

Awarded:$3,241,612 (Leadership 3)

‘New Knowledge and Research Capacity for Health Impacts of Global Environmental Change with Big Data, Novel Approach and New Technology’

Professor Yuming Guo

Faculty of Medicine, Nursing & Health Sciences

Awarded:$2,598,844 (Leadership 1)

‘Gold Electronic Skins for Remote Biodiagnostics’

Professor Wenlong Cheng

Faculty of Engineering

Awarded:$2,348,555 (Leadership 1)

‘Better treatments for autoimmune kidney disease and vasculitis’

Professor Arthur Kitching

Faculty of Medicine, Nursing & Health Sciences

Awarded:$2,297,570 (Leadership 2)

‘Decoding the drivers of food choices towards sustainable self-management of obesity’

Professor Antonio Verdejo-Garcia

Faculty of Medicine, Nursing & Health Sciences

Awarded:$2,248,555 (Leadership 1)

‘Improving evidence synthesis methods to enhance decision making about public health and policy interventions’

Associate Professor Joanne McKenzie

Faculty of Medicine, Nursing & Health Sciences

Awarded:$2,248,555 (Leadership 1)

‘Phosphatases in the pathogenesis of obesity and cancer’

Professor Tony Tiganis

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,927,015 (Leadership 3)

‘Harnessing the power of diverse data to model population impacts of injury and inform health and social policy’

Professor Belinda Gabbe

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,885,378 (Leadership 2)

‘Implementation research: Delivering impact at the interface between reproductive and metabolic women’s health’

Professor Helena Teede

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,870,806 (Leadership 3)

‘Health Risk Assessment of Bushfire Smoke on Children and Pregnancy Outcomes’

Doctor Shanshan Li

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,570,120 (Emerging Leadership 2)

Reducing Resuscitation Errors

Professor Mark Fitzgerald

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,500,000 (Leadership 2)

‘Unravelling the Contributions of Sleep Dysfunction to Alzheimer’s Disease and Dementia’

Associate Professor Matthew Pase

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,306,096 (Emerging Leadership 2)

‘Risk and resilience in Alzheimer’s pathogenesis, cognitive decline and clinical disease progression’

Associate Professor Yen Ying Lim

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,306,096 (Emerging Leadership 2)

‘Mitigating the consequence of preeclampsia for mother and child’

Doctor Kirsten Palmer

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,285,060 (Emerging Leadership 2)

‘Mitochondria live imaging in mammalian preimplantation embryos’

Doctor Jennifer Zenker

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,270,120 (Emerging Leadership 2)

‘Genetically defining and pharmacologically exploiting new oncogenic dependencies in Myc-driven lymphoid cancer’

Associate Professor Jake Shortt

Faculty of Medicine, Nursing & Health Sciences

Awarded:$1,228,048 (Emerging Leadership 2)

‘Precise medication use in people with Alzheimer’s disease’

Doctor Yijun Pan

Monash Institute of Pharmaceutical Sciences

Awarded:$650,740 (Emerging Leadership 1)

‘A personalised pharmacogenomic approach to inform autosomal dominant hypocalcaemia treatment’

Doctor Tracy Josephs

Monash Institute of Pharmaceutical Sciences

Awarded:$650,740 (Emerging Leadership 1)

‘Stereo-EEG and precision neuropsychology: optimising epilepsy surgery and minimising neurocognitive risk’

Doctor Andrew Neal

Faculty of Medicine, Nursing & Health Sciences

Awarded:$650,740 (Emerging Leadership 1)

‘Dissecting the impacts of the bacterial host versus plasmid on the AMR burden’

Doctor Margaret Lam

Faculty of Medicine, Nursing & Health Sciences

Awarded:$650,740 (Emerging Leadership 1)

‘Reducing medication-related harm in people living with dementia in residential aged care’ 

Doctor Amanda Cross

Centre for Medicine Use & Safety

Awarded:  $650,740 (Emerging Leadership 1)

‘Improving assisted reproductive technology outcomes – a personalised approach’

Doctor Rui Wang

Faculty of Medicine, Nursing & Health Sciences

Awarded:$650,740 (Emerging Leadership 1)

‘Defining the mechanisms that drive cell competition and plasticity in stomach cancer.’

Doctor Dustin Flanagan

Faculty of Medicine, Nursing & Health Sciences

Awarded:$650,740 (Emerging Leadership 1)

‘Understanding complex I assembly for better diagnosis and future treatment’

Doctor Luke Formosa

Faculty of Medicine, Nursing & Health Sciences

Awarded:$650,740 (Emerging Leadership 1)

‘Healthcare resource utilisation and long term outcomes following critical illness’

Doctor Alisa Higgins

Faculty of Medicine, Nursing & Health Sciences

Awarded:$613,240 (Emerging Leadership 1)

‘Transforming outcomes by investigating integrated treatments for methamphetamine use and trauma’

Doctor Shalini Arunogiri

Faculty of Medicine, Nursing & Health Sciences

Awarded:$450,370 (Emerging Leadership 1)

‘Improving Outcomes after  Extracorporeal Membrane Oxygenation’ 

Doctor Aidan Burrell

Faculty of Medicine, Nursing & Health Sciences

Awarded:$450,370 (Emerging Leadership 1)

‘Improving Neonatal Resuscitation’

Doctor Douglas Blank

Faculty of Medicine, Nursing & Health Sciences

Awarded:$450,370 (Emerging Leadership 1)

‘Cell Therapies for Newborn Infants: Translating Promise to Benefits‘ 

Doctor Atul Malhotra

Faculty of Medicine, Nursing & Health Sciences

Awarded:$431,671 (Emerging Leadership 1)

Centre for Research Excellence to transform outcomes of critically ill patients in ICU (CRE-ICU)

Led by Professor Carol Hodgson

Faculty of Medicine, Nursing and Health Sciences

Original article

Congratulations Jamie – NHMRC Investigator grant

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Congratulations to Jamie, Head of the Rossjohn / Immune Recognition lab, who has been named as a successful NHMRC Investigator (L3) grant holder  in the recent grant round (funding commencing 2022).

Investigator Grants is NHMRC’s flagship scheme which accounts for 40% of the Medical Research Endowment Account. It consolidates previously separate fellowship and research support into one grant scheme that provides researchers at all career stages with funding for their salary (if required) as well as a research support package over 5 years.

The objective of the Investigator Grant scheme is to support the research program of outstanding investigators at all career stages.

Original article and outcome of funding round available here.

We also extend our congratulations to all other grant awardees.

Listen to Erica’s interview with Vision Australia Radio

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Focal Point Podcast – 01 Sept 2021

A weekly program presented by Peter Greco, Focal Point covers services from blindness organisation (Eg. Vision Australia)  and other providers, technology, current affairs, breakthroughs in advocacy campaigns about all manner of challenges and promoting activities and events for people who are blind or vision impaired.

This week Peter Greco is talking to:

1 Isabel Osuna-Gatty – from the National Disability Coordination Office

2 Erica Tandori, Stuart Favilla – Talk about their multi-media experience “My Goodness” – (Skip to 15:59)

Available on the podcast, listen to the full song “My Goodness”.

Further information on the “My Goodness” Book can be found here.

The Vision Australia Radio Network incorporates ten community radio stations across Victoria, southern New South Wales, Adelaide and Perth and five digital radio services.

We offer a range of interesting and informative programs that feature readings from the latest newspapers, magazines and books.

Our exclusive specialist content includes programs on new technology, current affairs, book and film reviews, health and wellbeing, the arts, finance, travel and more.

Adapted from Original article.