Novel MHC Class I Structures on Exosomes

Sarah Lynch, Susana G. Santos, Elaine C. Campbell, Ailish M. S. Nimmo, Catherine Botting, Alan Prescott, Antony N. Antoniou, Simon J. Powis

    Research output: Contribution to journalArticlepeer-review

    44 Citations (Scopus)

    Abstract

    Exosomes are nanometer-sized vesicles released by a number of cell types including those of the immune system, and often contain numerous immune recognition molecules including MHC molecules. We demonstrate in this study that exosomes can display a significant proportion of their MHC class I (MHC I) content in the form of disulfide-linked MHC I dimers. These MHC I dimers can be detected after release from various cell lines, human monocyte-derived dendritic cells, and can also be found in human plasma. Exosome-associated dimers exhibit novel characteristics which include 1) being composed of folded MHC I, as detected by conformational-dependent Abs, and 2) dimers forming between two different MHC I alleles. We show that dimer formation is mediated through cysteine residues located in the cytoplasmic tail domains of many MHC I molecules, and is associated with a low level of glutathione in exosomes when compared with whole cell lysates. We propose these exosomal MHC I dimers as novel structures for recognition by immune receptors. The Journal of Immunology, 2009, 183: 1884-1891.

    Original languageEnglish
    Pages (from-to)1884-1891
    Number of pages8
    JournalJournal of Immunology
    Volume183
    Issue number3
    DOIs
    Publication statusPublished - 1 Aug 2009

    Keywords

    • MAJOR HISTOCOMPATIBILITY COMPLEX
    • UNFOLDED PROTEIN RESPONSE
    • CELL-DERIVED EXOSOMES
    • MONOCLONAL-ANTIBODIES
    • DENDRITIC CELLS
    • HEAVY-CHAINS
    • T-CELLS
    • HLA-G
    • HLA-B27
    • ANTIGEN

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