Formation of a nine-subunit complex by HLA class II glycoproteins and the invariant chain

Abstract

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 (I) 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. 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.