Late events in the intracellular sorting of major histocompatibility complex class II molecules are regulated by the 80-82 segment of the class II β chain

L. J. Tan, Stephanie Ceman, Alexander Chervonsky, Juan Rodriguez-Paris, Theodore L. Steck, Andrea J. Sant

Research output: Contribution to journalArticle

Abstract

The molecular mechanisms that regulate sorting of major histocompatibility complex (MHC) class II molecules into the endocytic pathway are poorly understood. For many proteins, access to endosomal compartments is regulated by cytosolically expressed sequences. We present evidence that a sequence in the lumenal domain of the MHC class II molecule regulates a very late event in class II biogenesis. Class II molecules containing single amino acid changes in the highly conserved 80-82 region of the β chain were introduced into invariant chain (Ii)-negative fibroblasts with wild-type α chain, and the derived transfectants were analyzed biochemically. Using an endosomal isolation technique, we have quantified the level of class II molecules expressed in endocytic compartments and found that in the absence of Ii, approximately 15% of total cellular class II molecules can be isolated from endosomal compartments. Mutation at position 80 enhances this localization, while changes at positions 81 and 82 ablate class II expression in endosomal compartments. In addition, we have evaluated whether the induced changes in intracellular distribution of class II molecules were due to alterations in early biosynthetic events, indicative of misfolding of the molecules, or to modulation of later trafficking events more likely to be a consequence of the modulation of a specific transport event. Despite the dramatic effects on endosomal localization induced by the mutations, early biosynthetic events and maturation of class II were unaffected by the mutations. Collectively, our data argue that late trafficking events that control the ability of the class II molecule to access antigens is regulated by the 80-82 segment of the MHC class II β chains.

Original languageEnglish (US)
Pages (from-to)1479-1488
Number of pages10
JournalEuropean Journal of Immunology
Volume27
Issue number6
DOIs
StatePublished - Jun 1 1997
Externally publishedYes

Keywords

  • Antigen presentation
  • Class II β chain
  • Endocytic compartment
  • Golgi

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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