SARS-CoV-2 peptide–HLA complex (SARS-CoV-2 pHLA)

SARS-CoV-2 peptide–HLA complexes are molecular assemblies formed on the surface of host cells following infection with the SARS-CoV-2 virus [1, 2]. These complexes consist of short viral protein fragments (peptides) bound within the groove of Human Leukocyte Antigen (HLA) molecules, which are the human version of the Major Histocompatibility Complex (MHC) [5, 6]. The primary biological function of these complexes is to present viral antigens to the immune system, specifically to T-cell receptors (TCRs) on CD8+ cytotoxic T cells (MHC class I) and CD4+ helper T cells (MHC class II) [2, 7]. This presentation is a critical step in the adaptive immune response, triggering the destruction of infected cells and the orchestration of long-term immunity [1, 13]. In the context of COVID-19, the repertoire of presented peptides—known as the immunopeptidome—determines the breadth and effectiveness of the T-cell response [2, 10]. Variations in HLA alleles among individuals influence disease susceptibility and severity, as some alleles present viral epitopes more effectively than others [5, 15, 18]. These complexes are primary targets for therapeutic intervention, including peptide-based vaccines such as CoVac-1 and adoptive T-cell therapies like CoV-2-STs or TCR-T cells, which aim to enhance or redirect the immune system to recognize and eliminate infected cells [20, 24, 25]. Challenges in targeting these complexes include viral escape through mutations in the peptide sequences and the requirement for HLA-matching in many T-cell-based therapies [14, 28, 33].

Other names

SARS-CoV-2 peptide–MHC complexSARS-CoV-2 pMHCSARS-CoV-2 immunopeptidomeSARS-CoV-2 T-cell epitopesSARS-CoV-2 pHLA complex

Presentation of viral epitopes to T-cell receptors (TCRs) to initiate adaptive immune responses, including CD8+ T-cell-mediated cytotoxicity and CD4+ T-cell-mediated help [2, 5, 7].