HLA-I and HLA-II Peptidomes of SARS-CoV-2: A Review

The adaptive (T-cell-mediated) immune response is a key player in determining the clinical outcome, in addition to neutralizing antibodies, after SARS-CoV-2 infection, as well as supporting the efficacy of vaccines. T cells recognize viral-derived peptides bound to major histocompatibility complexes (MHCs) so that they initiate cell-mediated immunity against SARS-CoV-2 infection or can support developing a high-affinity antibody response. SARS-CoV-2-derived peptides bound to MHCs are characterized via bioinformatics or mass spectrometry on the whole proteome scale, named immunopeptidomics. They can identify potential vaccine targets or therapeutic approaches for SARS-CoV-2 or else may reveal the heterogeneity of clinical outcomes. SARS-CoV-2 epitopes that are naturally processed and presented on the human leukocyte antigen class I (HLA-I) and class II (HLA-II) were identified for immunopeptidomics. Most of the identified SARS-CoV-2 epitopes were canonical and out-of-frame peptides derived from spike and nucleocapsid proteins, followed by membrane proteins, whereby many of which are not caught by existing vaccines and could elicit effective responses of T cells in vivo. This review addresses the detection of SARS-CoV-2 viral epitopes on HLA-I and HLA-II using bioinformatics prediction and mass spectrometry (HLA peptidomics). Profiling the HLA-I and HLA-II peptidomes of SARS-CoV-2 is also detailed.