BRLF1 peptide–Major Histocompatibility Complex (BRLF1-MHC)

The BRLF1 peptide–Major Histocompatibility Complex (MHC) is a molecular assembly found on the surface of cells infected with the Epstein-Barr virus (EBV) (UniProt: P03209). BRLF1, also known as Rta, is an immediate-early transcription factor that triggers the switch from viral latency to the lytic cycle. During this process, the BRLF1 protein is processed into peptides, such as the immunodominant YVLDHLIVV epitope, which are then presented by MHC class I molecules (typically HLA-A*02:01) to the immune system (PubMed: 9126268). This complex is a critical target for CD8+ cytotoxic T cells, which recognize the viral peptide and initiate the destruction of the infected cell. In clinical applications, the BRLF1-MHC complex is targeted using adoptive T-cell therapies and TCR-engineered cells to treat EBV-associated malignancies and lymphoproliferative disorders (PubMed: 30309861). Because BRLF1 is expressed at the very onset of the lytic phase, targeting this complex allows for the elimination of reservoir cells before they can release new viral particles.

Other names

Rta peptide-MHC complexEBV BRLF1-HLA complexBRLF1-HLA-A*02:01 complexEpstein-Barr virus R transactivator peptide-MHCBamHI R leftward reading frame 1 peptide-MHC

Targeting of the peptide-MHC complex by cytotoxic T lymphocytes or engineered receptors leads to the direct lysis of EBV-infected cells through the release of perforin and granzymes, or via antibody-dependent cellular cytotoxicity (ADCC) when using TCR-like antibodies.