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MHC and antigen in exosomes

Exosomes (top) containing antigen and MHC are shot out of B cells that meet partner T cells. ROCHE/EMBO

T cells tell B cells to spit out exosomes loaded with T cell stimulants, report Aura Muntasell, Adam Berger, and Paul Roche (NIH, Bethesda, MD).

Exosomes are the membrane pockets that lie within larger vesicles called multivesicular bodies (MVBs). In B cells and other antigen-presenting cells, MVBs and exosomes house antigens in complex with the MHC class II molecules that present them to T cells. When an MVB fuses with the plasma membrane, MHC-antigen from the MVB membrane is displayed on the B cell surface, while the exosome allotment of MHC-antigen is sent out into the extracellular environment.

In the new study, the authors found that a B cell shot out twice as many exosomes when it met a T cell that recognized its antigen. In turn, the exosomes stimulated the T cells to divide rapidly and make cytokines that further activate B cells.

The resulting T cell progeny also need to see antigen to be activated. Roche wondered, "How are those daughters getting stimulated from one lone B cell?" He imagines that the exosome secretion speeds the process.

"We think of it like a shotgun blast," says Roche. "The T cell tells the B cell to shoot out its exosomes, and they help activate the new T cells." Testing the theory will be difficult, however. "No one knows what exosomes do in real life; we have not been able to stop a cell from secreting them without killing it."

The signal to release exosomes seems to stem from the MHC molecule, probably upon binding to the T cell receptor. Artificially cross-linking MHC molecules also stimulated the release. Downstream tyrosine kinases were also required, but more signaling details are so far unavailable.

Exosomes acquired their MHC-antigen pairs via recycling from the cell surface. Perhaps sending out the exosomes saves recycled MHC-antigen from its alternative fate—lysosomal degradation. After all, once an enemy is found, MHC weapons are in high demand.

Reference:

Muntasell, A., et al. 2007. EMBO J. doi:10.1038/sj.emboj.7601842.[Medline]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 872K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?