Peptide loading in the endoplasmic reticulum accelerates trafficking of peptide:MHC class II complexes in B cells

In a combination of biochemical and immunoelectron-microscopical approaches we studied intracellular trafficking and localization of the endoplasmic-reticulum (ER)-formed complexes of murine MHC class II molecule I-A(b) and an antigenic peptide E alpha 52-68 covalently linked to its beta-chain, The association with the peptide in the ER leads to sharp acceleration of the intracellular trafficking of the complexes to the plasma membrane. Within the cells, E alpha 52-68:I-A(b) complexes accumulate in the multivesicular MHC class ii compartment (MIIC), but not in denser multilaminar or intermediate type MIICs, The changes in the trafficking of ER-formed complexes result solely from the presence of the tethered peptide, since wild-type class II molecules traffic similarly in bare lymphocyte syndrome cells and in wild-type antigen-presenting cells.