Defects in HLA class I antigen processing and presentation associated with BL. Cytosolic proteins are ubiquitinated, marking them for proteasomal degradation. Peptides generated from proteasomal degradation are then transported into the endoplasmic reticulum (ER) lumen by TAP (transporter associated with Ag presentation) and loaded onto HLA class I proteins. These class I peptide complexes are transported through the Golgi network to the cell surface for presentation to CD8+ T cells. The EBV EBNA1 protein contains a Gly/Ala repeat that impairs its proteasomal processing, resulting in the generation of peptides that are not readily accessible to class I molecules. Thus, peptides generated from EBNA1 proteins are unable to activate CD8+ T cells in the context of HLA class I molecules.
