ROLES FOR CALRETICULIN AND A NOVEL GLYCOPROTEIN, TAPASIN, IN THE INTERACTION OF MHC CLASS-I MOLECULES WITH TAP

Assembly of MHC class I-beta(2) microglobulin (beta(2)m) dimers in the endoplasmic reticulum involves two chaperones. Calnexin has previousl y been shown to interact with free class I heavy chains. Here, we show that the related chaperone, calreticulin, binds human class I-beta(2) m dimers prior to peptide loading. Calreticulin remains associated wit h at least a subset of class I molecules when they, in turn, bind to T AP. Further evidence suggests that the interaction of class I-beta(2)m dimers with TAP occurs via a novel uncharacterized 48 kDa glycoprotei n, tapasin, which can bind independently to TAP and class I-beta(2)m-c alreticulin complexes. Tapasin is absent from the mutant cell line .22 0, in which class I-TAP association and peptide loading is defective.