Human leukocyte antigen class I and class II molecules presenting Epstein-Barr virus polyepitope and gp350 peptides (HLA-EBV-pMHC)

The target consists of Human Leukocyte Antigen (HLA) class I and class II molecules presenting specific peptides derived from the Epstein-Barr virus (EBV) polyepitope (EBVpoly) and the gp350 glycoprotein. HLA molecules are cell-surface glycoproteins that play a central role in the immune system by presenting processed peptide fragments to T cells; class I molecules present to CD8+ cytotoxic T cells, while class II molecules present to CD4+ helper T cells (Hislop et al., 2007, Annual Review of Immunology). EBVpoly is a synthetic polyepitope construct designed to include multiple immunodominant CD8+ T-cell epitopes from various EBV latent proteins such as EBNA1, LMP1, and LMP2, while gp350 is the primary envelope protein of EBV and a major target for immune recognition (Smith et al., 2012, Blood; Thorley-Lawson, 2001, Nature Reviews Immunology). This peptide-MHC (pMHC) complex is the therapeutic target for EBV-specific T-cell therapies (VSTs), such as Tabelecleucel, which are engineered or selected to recognize these specific viral signatures on infected or malignant cells (Prockop et al., 2020, JCI). Targeting these complexes allows for the precise elimination of EBV-positive cells in conditions like post-transplant lymphoproliferative disorder (PTLD) and nasopharyngeal carcinoma. Therapeutic efficacy depends on the patient's HLA profile and the stable expression of viral antigens, while challenges include potential immune evasion by the virus through HLA downregulation.

Other names

MHC-EBV peptide complexEBV-specific peptide-HLA complexEBVpoly-gp350-HLA complexpMHC-EBV

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, triggering cytotoxic T-lymphocyte (CTL) activation and targeted lysis of EBV-infected cells.