Severe acute respiratory syndrome coronavirus 2 antigen-derived peptide–human leukocyte antigen complex (SARS-CoV-2 pHLA complex)

The SARS-CoV-2 antigen-derived peptide–human leukocyte antigen (pHLA) complex is a fundamental component of the adaptive immune system's response to COVID-19. It consists of a short viral peptide, typically 8-11 amino acids for Class I or longer for Class II, nestled within the binding groove of an HLA molecule on the cell surface (Nature Communications, 2021). These peptides are generated from the proteolytic cleavage of viral proteins like Spike, Nucleocapsid, and Orf1ab within infected cells (Cell Reports, 2020). The primary function of the pHLA complex is to serve as a ligand for T-cell receptors (TCRs), allowing the immune system to distinguish infected cells from healthy ones. Recognition of these complexes by CD8+ T cells triggers the release of perforins and granzymes, leading to the apoptosis of the infected host cell (Immunity, 2020). In drug development, these complexes are the primary targets for TCR-engineered T-cell (TCR-T) therapies and peptide-based vaccines aimed at eliciting robust cellular immunity (Frontiers in Immunology, 2022). However, therapeutic targeting is complicated by the vast diversity of HLA alleles across the human population and the potential for the virus to evolve mutations that escape HLA binding or TCR recognition (Science Immunology, 2021). Additionally, safety concerns include potential cross-reactivity with self-peptides, which could lead to unintended autoimmune damage (Journal of Clinical Investigation, 2021).

Other names

SARS-CoV-2 peptide-MHC complexSARS-CoV-2 pMHCCOVID-19 antigen-presenting complexSARS-CoV-2 peptide-HLA

Recognition by T-cell receptors (TCRs) to induce cytotoxic T-lymphocyte (CTL) mediated killing of infected cells or cytokine production by helper T cells.