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Interaction of HLA-DR and CD74 at the cell surface of antigen-presenting cells by single particle image analysis

Research output: Contribution to journalArticle

Author(s)

  • Ioannis Karakikes
  • Ian E G Morrison
  • Peter O'Toole
  • Gergana Metodieva
  • Cristina V Navarrete
  • Jesus Gomez
  • Jose M Miranda-Sayago
  • Richard J Cherry
  • Metodi Metodiev
  • Nelson Fernandez

Department/unit(s)

Publication details

JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
DatePublished - Dec 2012
Issue number12
Volume26
Pages (from-to)4886-4896
Original languageEnglish

Abstract

Major histocompatibility complex (MHC) class II-associated antigen presentation involves an array of interacting molecules. CD74, the cell surface isoform of the MHC class II-associated invariant chain, is one such molecule; its role remains poorly defined. To address this, we have employed a high-resolution single-particle imaging method for quantifying the colocalization of CD74 with human leukocyte antigen (HLA)-DR molecules on human fibroblast cells known for their capacity to function as antigen-presenting cells. We have also examined whether the colocalization induces internalization of HLA-DR using HA(307-319), a "universal" peptide that binds specifically to the peptide-binding groove of all HLA-DR molecules, irrespective of their alleles. We have determined that 25 ± 1.3% of CD74 and 17 ± 0.3% of HLA-DR are colocalized, and the association of CD74 with HLA-DR and the internalization of HLA-DR are both inhibited by HA(307-319). A similar inhibition of HLA-DR internalization was observed in freshly isolated monocyte-derived dendritic cells. A key role of CD74 is to translocate HLA-DR molecules to early endosomes for reloading with peptides prior to recycling to the cell surface. We conclude that CD74 regulates the balance of peptide-occupied and peptide-free forms of MHC class II at the cell surface.

    Research areas

  • Adult, Algorithms, Antigen-Presenting Cells, Antigens, Differentiation, B-Lymphocyte, Cell Line, Cell Membrane, Cells, Cultured, Dendritic Cells, Endocytosis, Flow Cytometry, Fluorescence Resonance Energy Transfer, HLA-DR Antigens, Hemagglutinin Glycoproteins, Influenza Virus, Histocompatibility Antigens Class II, Humans, Imaging, Three-Dimensional, Microscopy, Confocal, Microscopy, Fluorescence, Peptide Fragments, Protein Binding

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