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

Nature. 1991 Dec 5;354(6352):392-4. doi: 10.1038/354392a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Differentiation, B-Lymphocyte*
  • Cell Line
  • Cytoplasm / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • HLA-D Antigens / chemistry*
  • HLA-D Antigens / metabolism
  • Histocompatibility Antigens Class II / chemistry*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • In Vitro Techniques
  • Macromolecular Substances
  • Molecular Structure
  • Monensin / pharmacology
  • Protein Binding


  • Antigens, Differentiation, B-Lymphocyte
  • HLA-D Antigens
  • Histocompatibility Antigens Class II
  • Macromolecular Substances
  • invariant chain
  • Monensin