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-IA 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.
Hitzel
C
C
Division of Immunobiology, University of Bonn, Germany.
Kanzler
H
H
König
A
A
Kummer
M P
MP
Brix
K
K
Herzog
V
V
Koch
N
N
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D003545:Cysteine; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013954:Thyroglobulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; C045084:invariant chain; D013954:Thyroglobulin; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534280:Ctsl protein, rat; D003545:Cysteine