Figure 7.

Comprehensive scheme of endocytic compartments and class II trafficking in B cells. The proposed relation between the different types of endocytic compartments (1–6) including early and late MIICs as described in this study, and the classical terminology of endosomes and lysosomes are indicated. From our present morphological observations and the kinetic data in several recent fractionation studies (see Discussion), the following model of class II transport can be put forward. Class II/I-chain complexes derived from the TGN are transported to early MIICs and possibly to a minor extent to the plasma membrane and other endocytic compartments (see arrows with different thicknesses radiating from the TGN). After arrival in the endocytic pathway, class II/I-chain complexes migrate farther down the endocytic route (see arrows between types 1–6) together with endocytosed antigens, meanwhile being exposed to increasing proteolytic activity. This activity results in the removal of I-chain, a process probably already starting in type 3/early MIICs and progressing in later compartments. Once class II is freed from the I-chain peptide CLIP, antigenic peptides can bind to the class II molecules, a process catalyzed by HLA-DM. Peptide loading of class II commences in early MIICs and proceeds in later compartments, possibly depending on the type of class II and antigen. Escape of class II–peptide complexes from the degradative route for deposition at the cell surface has been shown to occur by exocytosis of MIICs by which the limiting membrane of MIICs is incorporated in the plasma membrane. During this process the internal vesicles of MIICs are externalized as exosomes (43). Other pathways of class II/peptide transport to the cell surface may very well exist but have not yet been identified.