Stable surface expression of invariant chain prevents peptide presentation by HLA-DR

Paul A. Roche, Christina L. Teletski, David R. Karp, Valérie Pinet, Oddmund Bakke, Eric O. Long

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Class II major histocompatibility complex (MHC) molecules are cell surface glycoproteins that bind and present immunogenic peptides to T cells. Intracellularly, class II molecules associate with a polypeptide referred to as the invariant (Ii) chain. Ii is proteolytically degraded and dissociates from the class II complex prior to cell surface expression of the mature class II αβ heterodimer. Using human fibroblasts transfected with HLA-DR1 and Ii cDNAs, we now demonstrate that truncation of the cytoplasmic domain of Ii results in the failure of Ii to dissociate from the αβIi complex and leads to stable expression of class II αβIi complexes on the cell surface. Furthermore, biochemical analysis and peptide presentation assays demonstrated that transfectants with stable surface αβIi complexes expressed very few free αβ heterodimers at the surface and were very inefficient in their ability to present immunogenic peptides to T cells. These results support the hypothesis that the cytoplasmic domain of Ii is responsible for endosomal targeting of αβIi and directly demonstrate that association with Ii interferes with the antigen presentation function of class II molecules.

Original languageEnglish (US)
Pages (from-to)2841-2847
Number of pages7
JournalEMBO Journal
Volume11
Issue number8
StatePublished - Jan 1 1992

Keywords

  • Antigen presentation
  • Endosome
  • HLA-DR
  • Intra-cellular traffic
  • Invariant chain

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Roche, P. A., Teletski, C. L., Karp, D. R., Pinet, V., Bakke, O., & Long, E. O. (1992). Stable surface expression of invariant chain prevents peptide presentation by HLA-DR. EMBO Journal, 11(8), 2841-2847.