Peptide-MHC complexes presenting Epstein-Barr virus antigens (EBV pMHC)

Peptide-MHC (pMHC) complexes presenting Epstein-Barr virus (EBV) antigens are essential molecular structures for the immune recognition of EBV-infected and transformed cells. These complexes are formed when viral proteins, such as Epstein-Barr nuclear antigen 1 (EBNA1) or latent membrane proteins (LMP1 and LMP2), are processed into short peptides and loaded onto Human Leukocyte Antigen (HLA) Class I or Class II molecules (Taylor et al., Nat Rev Cancer, 2015). HLA Class I complexes present antigens to CD8+ cytotoxic T cells, while HLA Class II complexes present to CD4+ helper T cells, orchestrating a comprehensive immune response (Neefjes et al., Nat Rev Immunol, 2011). In EBV-associated diseases, including post-transplant lymphoproliferative disorder (PTLD) and various lymphomas, these pMHC complexes serve as the primary targets for adoptive cell therapies like Tabelecleucel (Prockop et al., J Clin Invest, 2020). Therapeutic strategies involve using EBV-specific T cells or TCR-engineered cells that specifically bind these pMHC targets to induce apoptosis in malignant cells. These targets are also the focus of therapeutic vaccines designed to enhance the endogenous T-cell response against EBV-driven malignancies (Hui et al., Front Immunol, 2019). However, the high polymorphism of HLA alleles across the human population requires precise HLA matching for many of these therapies to be effective. Additionally, the potential for viral immune evasion through the downregulation of MHC molecules or antigen processing machinery remains a significant hurdle in clinical development.

Other names

EBV peptide-HLA complexesEpstein-Barr virus antigen-MHC complexesEBV-pMHCHLA-restricted EBV antigensEBV-specific peptide-MHC complexes

Recognition by T-cell receptors (TCRs) on cytotoxic and helper T-cells, leading to targeted lysis of EBV-infected or transformed cells and the release of pro-inflammatory cytokines.