Structure-Based Modeling of SARS-CoV-2 Peptide/HLA-A02 Antigens

Front Med Technol. 2020 Nov 17;2:553478. doi: 10.3389/fmedt.2020.553478. eCollection 2020.


SARS-CoV-2-specific CD4 and CD8 T cells have been shown to be present in individuals with acute, mild, and asymptomatic Coronavirus disease (COVID-19). Toward the development of diagnostic and therapeutic tools to fight COVID-19, it is important to predict and characterize T cell epitopes expressed by SARS-CoV-2. Here, we use RosettaMHC, a comparative modeling approach which leverages existing structures of peptide/MHC complexes available in the Protein Data Bank, to derive accurate 3D models for putative SARS-CoV-2 CD8 epitopes. We outline an application of our method to model 8-10 residue epitopic peptides predicted to bind to the common allele HLA-A*02:01, and we make our models publicly available through an online database ( We further compare electrostatic surfaces with models of homologous peptide/HLA-A*02:01 complexes from human common cold coronavirus strains to identify epitopes which may be recognized by a shared pool of cross-reactive TCRs. As more detailed studies on antigen-specific T cell recognition become available, RosettaMHC models can be used to understand the link between peptide/HLA complex structure and surface chemistry with immunogenicity, in the context of SARS-CoV-2 infection.

Keywords: MHC-I; SARS-CoV-2; T cell epitopes; epitope cross-reactivity; epitope-based vaccine; rosetta.