Human leukocyte antigen-restricted Epstein-Barr virus nuclear antigen 1-derived peptide–major histocompatibility complex (EBNA1-pMHC)

Human leukocyte antigen-restricted Epstein-Barr virus nuclear antigen 1-derived peptide–major histocompatibility complex (pMHC) refers to the presentation of specific fragments of the EBNA1 protein by HLA molecules on the surface of infected or malignant cells [Long et al., 2011, Journal of Experimental Medicine]. EBNA1 is a multifunctional viral protein essential for the replication and persistence of the Epstein-Barr virus (EBV) episome, and it is uniquely expressed in all EBV-associated malignancies, including nasopharyngeal carcinoma and various lymphomas [Young et al., 2016, Nature Reviews Cancer]. While EBNA1 possesses an internal glycine-alanine repeat domain that limits its proteasomal processing and subsequent MHC Class I presentation, specific epitopes are nonetheless presented and can be recognized by the immune system [Levitskaya et al., 1995, Nature]. These pMHC complexes serve as highly specific therapeutic targets for TCR-like antibodies and TCR-engineered T-cell therapies, which aim to bypass the virus's immune evasion mechanisms [Simovic et al., 2020, Frontiers in Immunology]. By targeting the pMHC rather than the intracellular protein directly, these therapies can selectively eliminate EBV-positive tumor cells while sparing healthy, non-infected tissue [Tang et al., 2022, Nature Communications]. Current research also explores the role of these complexes in autoimmune conditions, as molecular mimicry between EBNA1 peptides and host proteins has been implicated in the pathogenesis of multiple sclerosis [Bjornevik et al., 2022, Science].

Other names

EBNA1-HLA complexEBV EBNA1 peptide-MHCHLA-restricted EBNA1 antigenEBNA1-derived pMHCEpstein-Barr virus nuclear antigen 1 peptide-HLA complex

Targeted cell lysis via T-cell receptor (TCR) or TCR-like antibody recognition of the specific EBNA1 peptide fragment presented within the HLA groove on the cell surface [Simovic et al., 2020, Frontiers in Immunology].