Expression of invariant chain can cause an allele-dependent increase in the surface expression of MHC class I molecules

Adrian J. Reber, Heth R. Turnquist, Heather J. Thomas, Charles T. Lutz, Joyce C. Solheim

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Invariant chain (Ii) has been shown to play a significant part in the assembly of MHC class II molecules. Ii also binds to MHC class I, although it is not known when this first occurs or whether it can affect class I assembly. Our examination of lysates of Ld-transfected T2 cells showed that Ii bound intracellularly to folded, but not to open, forms of MHC class I. Furthermore, addition of peptides to the lysates dissociated Ii from the Ii-folded MHC class I complex. Thus, unlike other known chaperones, Ii associates only with folded, peptide-free class I molecules. To determine whether Ii can affect MHC class I transport and surface expression, we used both wild-type Ii and a mutant Ii that lacked the endosomal targeting sequence. Neither Ii nor IiΔ20 increased the rate of MHC class I migration; however, Ii and (to a greater extent) IiΔ20 increased cell surface expression of MHC class I. In HeLa cells, this effect was allele-specific, affecting HLA-A28 more than -B75. Ii also increased the surface expression of Kb more than Db on Panc02 pancreatic adenocarcinoma cells. Neither form of Ii was detectable at the cell surface with MHC class I, indicating that Ii had exercised its effect on class I intracellularly. In total, these data suggest that Ii can bind peptide-free folded class I/β2m heterodimers, but not open MHC class I heavy chains, in the endoplasmic reticulum, and that Ii can facilitate the surface expression of the MHC class I molecule.

Original languageEnglish (US)
Pages (from-to)74-81
Number of pages8
JournalImmunogenetics
Volume54
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Antigen presentation
  • Antigen processing
  • Chaperones
  • Invariant chain
  • MHC
  • Polymorphism

ASJC Scopus subject areas

  • Immunology
  • Genetics

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