Early events in the assembly of major histocompatibility complex class II heterotrimers from their free subunits

Publisher Website
Google Scholar
Abstract
Endogenous antigen presentation by major histocompatibility complex class II molecules can be understood if class II αβ heterodimers bind peptide in the endoplasmic reticulum (ER) before they associate with the invariant chain (Ii). We have studied the assembly of class II molecules from the free α, β and Ii subunits to examine the existence of a class II αβ heterotrimer as an intermediate in the assembly of class II αβIi heterotrimers in the ER. In human kidney cell transfectants, the free class II α and β subunits and the class II αβ heterodimer are retained in the ER by association with the chaperonin immunoglobulin binding protein (BiP) and Ii is retained through its cytoplasmic tail. Co‐expression of Ii results in release of BiP from class II αβ complexes and exit of class II αβIi heterotrimers from the ER. We show that the cytoplasmic tail and the transmembrane region of the class II α and β chain is not essential for proper assembly of the class II αβ heterodimer. We followed assembly of the class II αβIi heterotrimers in wild‐type cells. The class II subunits assemble post‐translationally. No class II αβ heterodimers could be isolated as intermediates in the formation of class II αβIi heterotrimers, suggesting that peptide binding by class II molecules in the ER is necessarily inefficient.