Proteolysis in MHC Class II Antigen Presentation José A Villadangos, Hidde L Ploegh  Immunity  Volume 12, Issue 3, Pages 233-239 (March 2000) DOI: 10.1016/S1074-7613(00)80176-4

Figure 1 MHC Class II Trafficking and Maturation in the Endocytic Route The αβIi complexes exit the endoplasmic reticulum (ER), traverse the Golgi, and enter the endocytic compartments directly or after transient expression at the plasma membrane. The relative amount of αβIi complexes that intersect the endocytic route at early endosomal, late endosomal, or lysosomal stations probably varies among differet types of APC. Conversion of αβIi into αβ-peptide can occur along the entire endocytic route. A mechanism independent of cysteine proteases and H-2DM/HLA-DM eliminates Ii in early endosomes (EE), enabling some αβ dimers first to capture high molecular weight polypeptides and then to mature into αβ-peptide. Most αβIi complexes proceed to later compartments where Ii is eliminated in a stepwise manner by as yet unknown proteases to generate αβ-Iip10. This complex is transformed into αβ-CLIP by the action of Cat S (in B cells and DC)/Cat L (in TEC). CLIP is then substituted by antigenic peptides in a reaction catalyzed by H-2DM/HLA-DM and H-2DO/HLA-DO. A schematic representation of the αβIi/Iip41, αβ-Iip10, and αβ-CLIP complexes is shown at the bottom. Immunity 2000 12, 233-239DOI: (10.1016/S1074-7613(00)80176-4)

Figure 2 Protease Specificity in the Generation of Antigenic Peptides Left: class II molecules may capture antigenic epitopes included in long polypeptide precursors. Several proteases would subsequently trim the unprotected regions. This mechanism would not require any particular protease, as long as cleavage occurs. Right: the generation of the epitopes shown requires the participation of one or more distinct proteases. In the absence of A, no epitope will be generated; the absence of either B or C prevents the formation of “circle” without affecting “square”; “triangle” is not generated unless B is inactive and requires D. Intermediate situations between the “Protease Dependent” (i.e., requiring a specific [set of] protease[s]) and the “Protease Independent” (i.e., not requiring any particular protease) scenarios might also exist. Immunity 2000 12, 233-239DOI: (10.1016/S1074-7613(00)80176-4)