Figure 1

Invariant chain (Ii) undergoes stepwise C-terminal degradation to generate class II-associated invariant chain peptide (CLIP), which occupies the peptide-binding groove of major histocompatibility complex (MHC) class II molecules until its exchange with antigen peptides. The figure depicts distinct intermediates in Ii chain processing, leading to the formation of CLIP. Ii undergoes progressive carboxy-terminal processing within endosomes by distinct cysteine proteases to generate CLIP. The enzymes responsible for the generation of Iip24 and Iip10 remain to be defined, although in purified form cathepsin S can generate CLIP from intact Ii. Mice deficient in cathepsin S accumulate Iip10 but not Ii or Iip24 in their B cells and dendritic cells, implying that additional important enzymes in this process remain to be defined.