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

Structure of HLA/A2S269277. H-bonding interactions (purple sticks and HLA-A2 cartoon) between the S269277 protein (peptide) and HLA-2 (cartoon). HLA-A2 contact residues are shown. H-bonds within the peptide's 3.5 range are also shown (light blue dots and black dashes). HLA, human leukocyte antigen. Credit: DOI: 10.1016/j.jbc.2021.101065
When individuals become infected by the SARS-CoV-2 viruses, their immune system plays a vital role in resolving COVID-19. The vaccines being given to millions of people around the world are intended to 'pre-warn' and arm the immune system, so that individuals infected by SARS-CoV-2 are less likely to die or develop severe illness. Two vital arms of the immune system play a key role in this, which are B cells and T cells.

Although we now have a molecular understanding about how antibodies (produced by B cells) can bind to and neutralize the spike proteins from SARS-CoV-2, researchers didn't know how T cell receptors, which are located on T cells, recognise antigens that are caused by the spike protein.

T cells are important in the protection against severe acute respiratory infections and SARS-CoV-2 vaccine. T cells from COVID-19 were previously studied, but the molecular basis for TCR recognition of SARS/CoV-2 remains unknown. It was a pleasure to work with the Monash University team and understand how T cells recognize antigens from SARS-CoV-2," stated Katherine Kedzierska, University of Melbourne laboratory head at The Peter Doherty Institute for Infection and Immunity.

The world's first discovery was made by Dr. Priyanka Chanrasia of Monash University, Dr. Jan Petersen, Professor Jamie Rossjohn, as well as Professor Kedzierska. They examined the TCR response to a spike protein fragment presented by an immune molecule called Human Leukocyte Antigen A2 or HLA-A2. The Australian Synchrotron was used in this work. It was published in Journal of Biological Chemistry.

"This is just one piece of a much larger puzzle. While SARS-CoV-2 is still evolving, we need to improve our understanding of how immune responses work," Dr. Jan Petersen said.

This team has important molecular insights into how T cells in the human immune system react to SARS-CoV-2. This work provides fundamental insights into the immune responses of different individuals to SARS-CoV-2.

Further information: Priyanka Chanrasia et. al., Structural basis of biased receptor recognition of an immunodominant HLA–A2 epitope of SARS-CoV-2's spike protein, Journal of Biological Chemistry (2021). Journal Information: Journal of Biological Chemistry Priyanka Chanrasia et. al., Structural basis of biased receptor recognition of an immunodominant HLA-2 epitope of SARS-CoV-2's spike protein, (2021). DOI: 10.1016/j.jbc.2021.101065