Epstein-Barr virus antigen-derived peptides presented by Human Leukocyte Antigen (HLA) class I and II (EBV pMHC)

Epstein-Barr virus (EBV) latency and lytic antigen-derived peptides presented by Human Leukocyte Antigen (HLA) class I and II are the primary targets for cellular immunotherapy against EBV-associated diseases. These targets consist of viral protein fragments, such as those from EBNA1, LMP1, LMP2, or BZLF1, which are processed intracellularly and displayed on the cell surface by HLA molecules (Taylor et al., 2015, Vaccine). The resulting peptide-HLA (pMHC) complex is specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells and CD4+ helper T cells (Cohen, 2000, NEJM). In EBV-transformed cells, such as those in nasopharyngeal carcinoma or post-transplant lymphoproliferative disorder (PTLD), these complexes act as neoantigens that allow the immune system to distinguish malignant cells from healthy tissue (Bollard & Heslop, 2014, Adv Exp Med Biol). Therapeutic interventions like tabelecleucel utilize allogeneic EBV-specific T cells to target these complexes and induce apoptosis in infected cells (Prockop et al., 2022, Lancet Oncology). Additionally, these targets are being explored in the context of autoimmune diseases like multiple sclerosis, where EBV-infected B cells are hypothesized to play a pathogenic role (Bjornevik et al., 2022, Science). Challenges in targeting these complexes include the high diversity of HLA alleles across populations and the potential for viral immune evasion through HLA downregulation. The specificity of these targets makes them ideal for reducing off-target toxicity compared to traditional chemotherapy.

Other names

EBV peptide-MHC complexesEBV-specific HLA-restricted antigensEBV latency/lytic antigen-HLA complexesEBV pMHC

Recognition of the viral peptide-HLA complex by T-cell receptors (TCRs) on cytotoxic or helper T cells, leading to targeted lysis of EBV-infected cells.