FORMATION OF A NINE-SUBUNIT COMPLEX BY HLA CLASS-II GLYCOPROTEINS AND THE INVARIANT CHAIN

HLA CLASS II molecules are heterodimeric transmembrane glycoproteins that bind and present processed antigenic peptides to CD4-positive T lymphocytes. Intracellularly, class II molecules associate with a third subunit termed the invariant (1) chain. Here we describe the physical characteristics of the intracellular class II alpha-beta-I complex. Chemical crosslinking, size exclusion chromatography and sedimentation velocity studies demonstrate that the alpha-beta-I complex is a nine-subunit transmembrane protein that contains three alpha-beta-dimers associated with an I chain trimer. The organization of class II alpha- and beta-subunits in such a multimer may have a role in the documented ability of the I chain to inhibit peptide binding to class II molecules 1-3. In addition, the formation of the nine-chain complex may induce the structural changes necessary to overcome the cytoplasmic retention signal responsible for the localization of free I chain in the endoplasmic reticulum, releasing class II-I chain complexes for transport to endosomes 4-6.