HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900798v1 183/3/1884    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Lynch, S. Articles by Powis, S. J. PubMed PubMed Citation Articles by Lynch, S. Articles by Powis, S. J.

Novel MHC Class I Structures on Exosomes¹

Sarah Lynch^*, Susana G. Santos^*, Elaine C. Campbell^*, Ailish M. S. Nimmo^*, Catherine Botting, Alan Prescott, Antony N. Antoniou and Simon J. Powis^2,*

^* Bute Medical School, University of St. Andrews, Fife, United Kingdom; Biomolecular Sciences, University of St. Andrews, Fife, United Kingdom; Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee, United Kingdom; and Division of Infection and Immunity, University College London, London, United Kingdom

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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ S.L. was funded by the University of St. Andrews Maitland-Ramsey studentship. A.M.S.N. was supported by bursaries from the Association of Physicians of Great Britain and Ireland and the Wolfson Trust. A.N.A. was supported by a U.K. Arthritis Research Campaign Fellowship.

² Address correspondence and reprint requests to Dr. Simon Powis, University of St. Andrews, Westburn Lane, St. Andrews, U.K. E-mail address: sjp10{at}st-andrews.ac.uk

³ Abbreviations used in this paper: MVB, multivesicular body; DC, dendritic cell; MHC I, MHC class I; ER, endoplasmic reticulum; β₂m, β₂-microglobulin; KIR, killer cell Ig-like receptor; LIR, leukocyte Ig-like receptor; AS, ankylosing spondylitis; TfR, transferrin receptor; GSH, glutathione; NEM, N-ethylmaleimide; pI, isoelectric point.