Immunological significances of invariant chain from the aspect of its structural homology with the cystatin family.

The primary structure of p31 of invariant chain (Ii-chain) shows about 50% homology with those of the cystatin family which are endogenous cysteine protease inhibitors. The binding domains between Ii-chain and HLA-DR-7 were estimated from the structural homology between cystatin and Ii-chain and also between cathepsins and DR-7, respectively. The QL64-71 and GS76-88 of Ii-chain were estimated to be the binding domains with GG45-51 and VS57-63 of HLA-DR7, respectively. The purified human Ii-chain from spleen is capable of forming four molecular forms from monomer to tetramer by redox-potential dependent disulfide bond formation. The Ii-chain inhibits cathepsin L and H competitively as a dimer and the K(i) value for cathepsin L was 4.1 x 10(-8) M, but cathepsin B was not inhibited at all. The Ii-chain showed mainly a dimer (60 kDa) under the assay condition of cathepsins with cysteine and was not degraded by these cathepsins. The Ii-chain may play an important role in the regulation of antigenic peptide presentation to MHC class II.