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 previously 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 with at least a subset of class I molecules when they, in turn, bind to TAP. Further evidence suggests that the interaction of class I-beta(2)m dimers with TAP occurs via a novel uncharacterized 48 kDa glycoprotein, tapasin, which can bind independently to TAP and class I-beta(2)m-calreticulin complexes. Tapasin is absent from the mutant cell line .220, in which class I-TAP association and peptide loading is defective.