WEHI-LTU ECR Seminar Exchange Program hosted by Dr Ashleigh Davey

Dr Demetra Chatzileontiadou

NHMRC Emerging Leadership Fellow, La Trobe Institute for Molecular Science (LIMS), La Trobe University

The association and molecular mechanism behind asymptomatic SARS-CoV-2 infection

L7W Seminar Room
Join via TEAMS
Including Q&A session

Throughout the COVID-19 pandemic, research has centred on understanding why some people infected with the SARS-CoV-2 virus experience severe disease. However, 10-30% of individuals with the virus do not show any symptoms. Investigating asymptomatic infection could shed light on features of the immune system that help to eliminate SARS-CoV-2. We recently showed that there is a strong association between Human Leukocyte Antigen (HLA)-B*15:01 and asymptomatic infection and that this genetic association is due to pre-existing T cell immunity. We also identified public, high affinity, cross-reactive T cell receptors (TCR) and hypothesised that they might provide the molecular basis for the HLA-B*15:01-mediated pre-existing immunity. Here, we reveal details of this molecular basis, including the crystal structure of the public TCR in complex with the NQKLIANQF peptide-HLA-B*15:01 which shows non-typical binding, explaining T cell cross-reactivity. Furthermore, we reveal significant differences in the T cell responses between HLA-B*15:01+ asymptomatic/mild infection compared to moderate/severe infection. Our findings have major implications for public health because such knowledge could inform the design and development of vaccines and therapies for COVID-19. More broadly, identifying genetic factors that control the course of the disease could begin to explain the wide variation in how people respond to SARS-CoV-2 and other viral infections.

Dr Demetra Chatzileontiadou is an NHMRC Emerging Leadership Fellow working at La Trobe University, Victoria, Australia. She was awarded her PhD with Distinction in Biochemistry and Molecular Biology from the University of Thessaly in Greece (November 2016). Immediately after completing her PhD, she was awarded a highly competitive international IKY Fellowship for excellence in her postgraduate studies, that supported her post-doctoral research for one year. In late 2017, Demetra moved to Australia, as a postdoctoral research fellow at Monash University and since 2021 at La Trobe University (La Trobe Institute for Molecular Science, LIMS). Since her PhD, she has driven multiple successful projects resulting in a deeper understanding of host-pathogens recognition. The key aim of Demetra’s research is to elucidate the molecular mechanisms that are involved in the immune system actions when faced with viral infections.

All welcome!