Defects in HLA class II antigen processing and presentation associated with BL. Extracellular Ags are endocytosed and degraded in increasingly acidified endolysosomal compartments. GILT helps in Ag/peptide processing by reducing disulfide bonds in the acidic environment. These peptides are further processed by acidic cathepsins for loading onto HLA class II proteins. HLA class II is synthesized in the ER lumen and forms a complex with Ii that is transported through the trans-Golgi network for processing by cathepsins in the endolysosomal compartments. Here Ii is degraded, leaving a fragment, CLIP, in the class II binding groove. HLA-DM mediates the release of CLIP and the loading of appropriate peptides onto HLA class II molecules. These complexes are then transported to the cell surface for presentation to CD4+ T cells. BL-associated inhibitory molecules (BLAIM) may interfere with functional class II presentation that perturbs CD4+ T cell recognition of BL.
