Poster Presentation The 46th Lorne Conference on Protein Structure and Function 2021

Structural characterization of SARS-CoV-2 peptides presented by Human Leukocyte Antigen molecules (#221)

Christopher Szeto 1 , Dimitra S.M. Chatzileontiadou 1 , Dhilshan Jayasinghe 1 , Andrea T. Nguyen 1 , Hannah Sloane 1 , Chris Lobos 1 , Hanim Halim 1 , Alan Tunnicliffe-Riboldi 2 , Emma J. Grant 1 , Stephanie Gras 1 3
  1. Monash University, Clayton, Victoria, Australia
  2. Australian Synchrotron, ANSTO, Clayton 3168, VIC, Australia
  3. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, VIC 3800, Australia

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 defense 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-CoV2 cause severe acute respiratory syndrome, other coronavirus strains (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. Using protein crystallography and X-ray diffraction, we have structurally characterized the presentation of SARS-CoV-2 peptides, which could influence vaccine strategies and provide a basis for research in T cell therapy.