Thyroglobulin type-I-like domains in invariant chain fusion proteins mediate resistance to cathepsin L digestion

The MHCII associated invariant chain isoform Ii41 shows homology to a repeat in thyroglobulin (TgR), We show that the Ii31 isoform, which lacks the TgR-like domain, is sensitive to cathepsin L treatment whereas Ii41 displays substantial resistance. The TgR-like sequence of Ii41 was exchanged for thyroglobulin type-LA and -IB repeats, that contain six or four cysteine residues, Resistance to cathepsin L digestion was maintained upon substitution of the Ii41 TgR for homologous sequences from TgR type-IA. Mutation of a conserved cysteine in the TgR domain of an Ii fusion protein strongly reduced resistance to cathepsin L digestion. (C) 2000 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.