Selective Enrichment of Tetraspan Proteins on the Internal Vesicles of Multivesicular Endosomes and on Exosomes Secreted by Human B-lymphocytes
Open accessAbstract
Association of major histocompatibility complex (MHC) class II molecules with peptides occurs in a series of endocytic vacuoles, termed MHC class II-enriched compartments (MIICs). Morphological criteria have defined several types of MIICs, including multivesicular MIICs, which are composed of 50-60-nm vesicles surrounded by a limiting membrane. Multivesicular MIICs can fuse with the plasma membrane, thereby releasing their internal vesicles into the extracellular space. The externalized vesicles, termed exosomes, carry MHC class II and can stimulate T-cells in vitro. In this study, we show that exosomes are enriched in the co-stimulatory molecule CD86 and in several tetraspan proteins, including CD37, CD53, CD63, CD81, and CD82. Interestingly, subcellular localization of these molecules revealed that they were concentrated on the internal membranes of multivesicular MIICs. In contrast to the tetraspans, other membrane proteins of MIICs, such as HLA-DM, Lamp-1, and Lamp-2, were mainly localized to the limiting membrane and were hardly detectable on the internal membranes of MIICs nor on exosomes. Because internal vesicles of multivesicular MIICs are thought to originate from inward budding of the limiting membrane, the differential distribution of membrane proteins on the internal and limiting membranes of MIICs has to be driven by active protein sorting.
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CD63 and CD9 are potential exosome markers; ARF6 and VAMP3 are proposed microvesicle markers; TSP and C3b are accepted apoptotic body markers; Gag protein may be an RLP marker.
“CD63 and CD9 are potential markers of exosomes [22, 117]. Markers of microvesicles are less well established though ARF6 and VCAMP3 are recently proposed [66]. TSP and C3b are generally accepted markers of apoptotic bodies. The RLPs are less well studied though Gag protein may be a marker for this group of EVs (Table 1).”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [22]
The citation is attached to the exosome-marker sentence, not the subsequent claims about other vesicle types. The Discussion (page unavailable) reports that CD63 is enriched on exosomes, supporting its use as a potential marker. The copy does not identify CD9 as an exosome marker (searched: CD9). (LLM, conf=0.86)
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- Authors
- Escola, J.-M., Kleijmeer, M. J., Stoorvogel, W., Griffith, J. M., Yoshie, O., & Geuze, H. J.
- Affiliations
- Utrecht University (NL)
- Shionogi (Japan) (JP)
- Corresponding author
- Geuze, Hans J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 273
- Issue
- 32
- Pages
- 20121-20127
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2028248159
- Cited by
- 1,228
- References
- 1
- Citations by year
- 2026: 30 · 2025: 51 · 2024: 85 · 2023: 66 · 2022: 76 · 2021: 96 · 2020: 60 · 2019: 60 · 2018: 57 · 2017: 49 · 2016: 50 · 2015: 43 · 2014: 50 · 2013: 61 · 2012: 44
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- multivesicular endosomes, exosomes, CD86, CD37, CD53, CD63, CD81, CD82, HLA-DM, LAMP1, LAMP2, B cells, membrane protein sorting, T cell costimulation
- MeSH terms
- Histocompatibility Antigens Class II, B-Lymphocytes, Exocytosis, HLA-D Antigens, Humans, Immunohistochemistry, Membrane Fusion, Membrane Glycoproteins, Membrane Proteins, Endosomes, T-Lymphocytes, Antigens, CD, Microscopy, Immunoelectron, Lysosomal Membrane Proteins, B7-2 Antigen
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