EARLY EVENTS IN THE ASSEMBLY OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II HETEROTRIMERS FROM THEIR FREE SUBUNITS

Endogenous antigen presentation by major histocompatibility complex cl ass II molecules can be understood if class II alpha beta heterodimers bind peptide in the endoplasmic reticulum (ER) before they associate with the invariant chain (Ii). We have studied the assembly of class I I molecules from the free alpha, beta and Ii subunits to examine the e xistence of a class II alpha beta heterodimer as an intermediate in th e assembly of class II alpha beta Ii heterotrimers in the ER. In human kidney cell transfectants, the free class II alpha and beta subunits and the class II alpha beta heterodimer are retained in the ER by asso ciation with the chaperonin immunoglobulin binding protein (BiP) and I i is retained through its cytoplasmic tail. Co-expression of Ii result s in release of BiP from class II alpha beta complexes and exit of cla ss II alpha beta Ii heterotrimers from the ER. We show that the cytopl asmic tail and the transmembrane region of the class II alpha and beta chain is not essential for proper assembly of the class II ap heterod imer. We followed assembly of the class II alpha beta Ii heterotrimers in wild-type cells. The class II subunits assemble post-translational ly. No class II alpha beta heterodimers could be isolated as intermedi ates in the formation of class II alpha beta Ii heterotrimers, suggest ing that peptide binding by class II molecules in the ER is necessaril y inefficient.