T cells are paramount to the adaptive immune system, more specifically in cellular immunity, when clearing infection upon activation. The central interaction of cell-mediated adaptive immunity is between the T cell receptor (TCR) and the presentation of an antigen bound by Human Leukocyte Antigen (HLA) molecule. The cytotoxic ability of CD8+ T cells, a subset of T cells, has garnered a lot of interest in how they can combat SARS-CoV-2 infection. Moreover, there is limited information on the CD8+ T cell cross-reactivity to pandemic and seasonal coronaviruses derived epitopes, despite its potential for therapeutics.
My project investigates the molecular mechanism of T cell cross-reactivity towards Nucleocapsid-derived peptides from pandemic and seasonal coronaviruses. We have discovered a SARS-CoV-2 Nucleocapsid-derived peptide, N105-113 (SPRWYFYYL), able to elicit strong T cell response from individuals expressing the HLA-B*07:02 allele, the 6th most common HLA-B allele in the world. The N105-113 sequence is highly conserved within the seasonal coronaviruses HCoV-OC43 and HCoV-HKU-1, (LPRWYFYYL).
We assessed the stability of peptide-HLA by performing thermal stability assays. The visualisation of the interaction of the SARS-CoV-2 and seasonal coronaviruses peptide binding in the HLA were then analysed using X-ray crystallography, and their interaction with the TCR were assessed using surface plasmon resonance.
My project especially focuses on T cell cross-reactivity in SARS-CoV-2 and seasonal coronaviruses to unravel the molecular mechanisms of T cell recognition to provide new avenues on how to better activate T cells that could be used in future vaccine designs or therapeutics.