¿p#1 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes COVID-19, remains a major global health threat. T cell immunity, particularly CD8 + cytotoxic T lymphocytes (CTLs), is essential for viral clearance and long-term protection. This study focused on CTL epitopes restricted by HLA-A11:01 and HLA-A02:01, using bioinformatic predictions and HLA transgenic mouse models to identify and validate immunodominant epitopes from SARS-CoV-2 structural proteins (S, E, M, N). Results showed strong correlation between predicted immunogenicity scores (NetMHCpan, NetCTLpan) and actual CTL responses for HLA-A11:01-restricted epitopes. HLA-A02:01-restricted epitopes showed more variable correlation, likely due to antigen processing differences and TCR repertoire diversity. Notably, 21 epitopes were highly conserved across twelve major SARS-CoV-2 variants, suggesting their potential as universal vaccine targets. Significant variability in CTL responses to selected epitopes was observed among COVID-19-recovered individuals, possibly influenced by antigen presentation efficiency. This supports epitope fingerprinting—a strategy that categorizes individuals based on their T cell memory breadth and intensity, with potential for enhancing vaccine efficacy assessments and identifying those with strong immune memory at reduced reinfection risk. This study provides experimental and theoretical insights supporting epitope-based SARS-CoV-2 vaccine optimization and targeted immunization strategies.