To date, the COVID-19 pandemic has claimed over a million lives and afflicted more than 40 million individuals. Although a global effort has been enacted for vaccine and drug discovery, our rudimentary understanding of SARS-CoV-2 infection and our own immune defence against this infection remains unclear. Our immune system can naturally overcome viral infection through the presentation of viral protein fragments or peptides (p) via human leukocyte antigen (HLA) molecules.
These peptide-HLA complexes (pHLAs) are recognized by cytotoxic T cells that can activate, proliferate, and kill infected cells. T cells also retain memory of their encounter with the virus, and will respond faster during re-infection. How peptides from coronavirus are presented on the cell surface by HLA molecules can impact T cell recognition and influence the outcome of viral clearance, and therefore, outcome of the disease.
Although SARS and SARS-CoV-2 cause severe acute respiratory syndrome, seasonal coronaviruses such as 229E, OCE43, HKU1, and NL63 only cause the common cold. These coronaviruses share protein homology that can also be presented by HLAs, meaning that prior exposure to a less severe strain of coronavirus may infer immunity via memory T cells if similar peptides are presented in the same structural fashion.
We used protein crystallography to further understand the presentation of SARS-CoV-2 peptides by HLA molecules, determine their stability which impact on T cell activation. In addition, we have determine the T cell response to those peptides, providing information that help map the epitopes from the virus that could influence vaccine strategies and provide a basis for research in T cell based vaccine.