IMMUNOLOGICAL SIGNIFICANCES OF INVARIANT CHAIN FROM THE ASPECT OF ITSSTRUCTURAL 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 c ysteine 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 Q L(64-71) and GS(76-88) of Ii-chain were estimated to be the binding do mains with GG(45-51) and VS57-63 of HLA-DR7, respectively. The purifie d human Ii-chain From spleen is capable of forming four molecular form s 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 cathe psin B was not inhibited at all. The Ii-chain showed mainly a dimer (6 0 kDa) under the assay condition of cathepsins with cysteine and was n ot degraded by these cathepsins. The Ii-chain may play an important ro le in the regulation of antigenic peptide presentation to MHC class II .