Novel MHC Class I Structures on Exosomes

TY - JOUR

T1 - Novel MHC Class I Structures on Exosomes

AU - Lynch, Sarah

AU - Santos, Susana G.

AU - Campbell, Elaine C.

AU - Nimmo, Ailish M. S.

AU - Botting, Catherine

AU - Prescott, Alan

AU - Antoniou, Antony N.

AU - Powis, Simon J.

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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.

AB - 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.

KW - MAJOR HISTOCOMPATIBILITY COMPLEX

KW - UNFOLDED PROTEIN RESPONSE

KW - CELL-DERIVED EXOSOMES

KW - MONOCLONAL-ANTIBODIES

KW - DENDRITIC CELLS

KW - HEAVY-CHAINS

KW - T-CELLS

KW - HLA-G

KW - HLA-B27

KW - ANTIGEN

U2 - 10.4049/jimmunol.0900798

DO - 10.4049/jimmunol.0900798

M3 - Article

C2 - 19596992

SN - 0022-1767

VL - 183

SP - 1884

EP - 1891

JO - Journal of Immunology

JF - Journal of Immunology

IS - 3

ER -