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Publication : Circulating, soluble forms of major histocompatibility complex antigens are not exosome-associated.

First Author  MacKay PA Year  2006
Journal  Eur J Immunol Volume  36
Issue  11 Pages  2875-84
PubMed ID  17072917 Mgi Jnum  J:117111
Mgi Id  MGI:3695629 Doi  10.1002/eji.200636041
Citation  MacKay PA, et al. (2006) Circulating, soluble forms of major histocompatability complex antigens are not exosome-associated. Eur J Immunol 36(11):2875-84
abstractText  In vitro studies have shown that soluble MHC (sMHC) released by cell lines is bound to nano-vesicles termed exosomes. It is thought that exosomes may represent the major reservoir of sMHC class I and II molecules in biological fluids. However, most studies have been confined to in vitro assays performed with cell lines. We show here that sMHC in the serum or plasma differs from exosome-bound sMHC in five ways: In contrast to exosome-associated sMHC, circulating sMHC is of low density, has a low apparent molecular mass (40-300 kDa) and is not detergent-labile. Moreover, the majority of MHC class II isoforms and MHC class I in blood are not physically linked and circulating HLA-DR is accessible to an antibody specific for the HLA-DR alpha-chain intracellular epitope, which is masked by its association with cellular or exosomal membranes. Finally, utilizing transcriptional activator of murine MHC class II (C2ta) promoter-mutant mice, we showed that the release of sMHC class II into the circulation is dependent on the C2ta pI promoter, but not pIII or pIV. This suggests that myeloid dendritic cells and/or macrophages, which preferentially use promoter pI of the C2ta gene, produce most of the sMHC class II found in the circulation.
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