Processing

MHC class II molecules are transported from the endoplasmic reticulum (ER) via the Golgi to endoso-mal compartments as a complex with invariant chain (Ii). The Ii prevents endogenous peptides from binding to the groove of MHC class II molecules. After removal of Ii in the acidic endosomal compartments, peptides are able to bind to the MHC groove. Pep-tide-loaded MHC class II molecules are then transported to the membrane surface for antigen presentation. The amino acid residues 81-104 of Ii, dubbed class Il-associated invariant-chain peptides (CLIP), remain bound to the class II antigen-binding grooves. In endosomal compartments, MHC class Il-like DM molecules promote the dissociation of CLIP from the MHC class II complex. Because cells can utilize a different mechanism for antigen presentation from other APCs, namely mlg-mediated antigen internalization, the antigen peptide loading of MHC class II in B lymphocytes is expected to take place in a compartment accessible to mlg. The process may occur in early and late endosomes and lysosomes. However, investigators have found compartments which are distinct from the conventional vesicles described above. These compartments for peptide loading (CPLs) meet several requirements for antigen loading vesicles in B cells (Figure 1). mlgG and mlgM efficiently enter the compartments, and transiently accumulated MHC class II molecules are evident. MHC class II molecules in these compartments are not associated with the Ii chain. Some of the MHC class II molecules are loaded with antigen peptides. Most newly synthesized MHC class II molecules are transported through CPLs on their way to the plasma membrane. These compartments are not accessible to the transferrin receptor. Morphologically, these compartments in B cells demonstrate a physical structure with an internal vesicle membrane similar to that seen in the multivesicular bodies, an intermediate in the conventional endosomal pathway. Antigen-presenting B cells may therefore be class II V7 Y T m'9

Golgi

Antigen

Antigen class II V7 Y T m'9

Golgi

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