Epstein-Barr virus BRLF1 peptide–Major Histocompatibility Complex (BRLF1 pMHC)

The BRLF1 peptide–Major Histocompatibility Complex (MHC) is a molecular assembly consisting of a peptide fragment derived from the Epstein-Barr virus (EBV) BRLF1 protein, also known as Rta, presented on the surface of infected cells by MHC class I molecules, most commonly HLA-A*02:01 (UniProt P03209; PMID: 15141007). BRLF1 is a key immediate-early transcription factor that initiates the viral lytic cycle, making it one of the first viral proteins expressed during reactivation from latency (PubMed: 10823858). This early expression makes the BRLF1 pMHC complex a critical target for the host immune system to identify and eliminate EBV-infected cells before the production of infectious virions. In the field of immunotherapy, this complex is targeted by adoptive T-cell therapies, including EBV-specific T cells (EBVSTs) and engineered TCR-T cells, to treat EBV-associated malignancies such as nasopharyngeal carcinoma, Burkitt lymphoma, and post-transplant lymphoproliferative disorder (PTLD) (Nature Communications: 10.1038/s41467-021-24345-2). Therapeutic interventions like Tabelecleucel utilize T cells that recognize these complexes to induce targeted cytotoxicity against malignant cells (Lancet Oncology: 10.1016/S1470-2045(22)00706-5). The specificity of the T-cell receptor (TCR) for the BRLF1 peptide–MHC complex is essential for ensuring robust anti-tumor activity while minimizing off-target effects on healthy tissues.

Other names

BRLF1-HLA complexRta peptide-MHCEBV BRLF1 pMHCHLA-A*02:01-restricted BRLF1 antigenImmediate-early protein R peptide-MHC

T-cell receptor (TCR) mediated recognition of the viral peptide-MHC complex on the target cell surface, leading to the formation of an immunological synapse and subsequent release of perforins and granzymes to induce apoptosis of the EBV-infected or malignant cell (PMID: 34210989).