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  • The EMBO Journal (2000) 19, 882 - 891
  • doi:10.1093/emboj/19.5.882

Early endosomal maturation of MHC class II molecules independently of cysteine proteases and H-2DM

José A. Villadangos2, Christoph Driessen1, Guo-Ping Shi3, Harold A. Chapman3 and Hidde L. Ploegh1

  1. Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
  2. Present address: Department of Immunology, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
  3. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA

Correspondence to:

Hidde L. Ploegh, E-mail: ploegh@hms.harvard.edu

Received 19 October 1999; Accepted 12 January 2000; Revised 12 January 2000

Major histocompatibility complex (MHC) class II molecules bind and present to CD4+ T cells peptides derived from endocytosed antigens. Class II molecules associate in the endoplasmic reticulum with invariant chain (Ii), which (i) mediates the delivery of the class II–Ii complexes into the endocytic compartments where the antigenic peptides are generated; and (ii) blocks the peptide-binding site of the class II molecules until they reach their destination. Once there, Ii must be removed to allow peptide binding. The bulk of Ii–class II complexes reach late endocytic compartments where Ii is eliminated in a reaction in which the cysteine protease cathepsin S and the accessory molecule H-2DM play an essential role. Here, we here show that Ii is also eliminated in early endosomal compartments without the intervention of cysteine proteases or H-2DM. The Ii-free class II molecules generated by this alternative mechanism first bind high molecular weight polypeptides and then mature into peptide-loaded complexes.

  • Keywords:

    • endosomes,
    • invariant chain,
    • MHC class II