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 αβI complex. Chemical crosslinking, size exclusion chromatography and sedimentation velocity studies demonstrate that the αβI complex is a nine-subunit transmembrane protein that contains three αβ dimers associated with an I chain trimer. The organization of class II α-and β-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.