Epstein-Barr virus nuclear antigen 1-derived peptide–Human leukocyte antigen class I complex (EBNA1-peptide–HLA-I complex)

The Epstein-Barr virus nuclear antigen 1 (EBNA1)-derived peptide–Human leukocyte antigen (HLA) class I complex is a specialized immunological target used in the treatment of EBV-associated malignancies and chronic infections (PMID: 31434705). EBNA1 is a viral protein required for the persistence and replication of the EBV genome in host cells and is the only viral protein expressed in all forms of EBV latency, including Latency I, II, and III (PMID: 25231358). Although EBNA1 contains a glycine-alanine repeat (GAr) domain that inhibits its own proteasomal processing to evade immune detection, specific peptides are successfully presented on HLA class I molecules, such as HLA-A*02:01 or HLA-B*35:01 (PMID: 15123769). Therapeutic interventions, including T-cell receptor (TCR)-engineered T cells and TCR-like antibodies, are designed to recognize these specific peptide-MHC complexes to induce targeted lysis of EBV-positive tumor cells (PMID: 32817593). This target is highly significant for conditions like nasopharyngeal carcinoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disorder (PTLD), where EBV plays a primary oncogenic role. By targeting the peptide-MHC complex, these therapies can address intracellular viral proteins that are otherwise inaccessible to standard antibody treatments.

Other names

EBNA1-MHC class I complexEBV EBNA1-HLA complexEBNA1-HLA-A*02:01 complexEBNA1-HLA-B*35:01 complex

Recognition of the peptide-MHC complex by T-cell receptors or TCR-like antibodies, triggering cytotoxic cell death of the target cell.