Immunogenic SARS-CoV2 Epitopes Defined by Mass Spectrometry.

Area of Science:

• Immunology
• Virology
• Proteomics

Background:

• SARS-CoV-2 infections trigger humoral and cellular immunity, with T cell responses critical for COVID-19 recovery and protection.
• Identifying immunogenic SARS-CoV-2 epitopes for T cell activation has been challenging, as in silico predictions often fail empirical validation.
• Current methods rely on predicted epitopes, lacking testing for actual immunogenicity in eliciting T cell responses against endogenous antigens.

Approach:

• Utilized MHC immune-precipitation, acid elution, and tandem mass spectrometry to define the SARS-CoV-2 immunopeptidome.
• Identified novel epitopes from structural and non-structural proteins, including membrane glycol-protein (MGP) and non-structural protein-13 (NSP13).
• Employed an endogenous T cell (ETC) workflow to empirically validate the immunogenicity of MS-defined peptides.

Key Points:

• Discovered novel SARS-CoV-2 epitopes from MGP and NSP13, conserved across strains and variants.
• Demonstrated that MS-defined epitopes, unlike in silico predictions, directly elicit T cell responses.
• Confirmed T cell recognition of MGP and NSP13 in cells endogenously expressing these viral antigens.

Conclusions:

• This study presents a novel approach to defining SARS-CoV-2 immunogenic epitopes by directly analyzing eluted peptides.
• Provides empirical evidence for the immunogenicity of newly identified MGP and NSP13 epitopes, crucial for understanding T cell-mediated immunity in COVID-19.
• The findings offer a more reliable strategy for identifying epitopes that can induce meaningful T cell responses for potential therapeutic and diagnostic applications.