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TCRs alive on the periphery

Phosphotyrosine signaling (purple) remains associated with TCR clusters (green) longer when TCRs are prevented (bottom) from moving inward. DUSTIN/AAAS

Keeping T cell receptors (TCRs) away from the center of the immunological synapse boosts stimulatory stignals, based on work from Kaspar Mossman, Gabriele Campi, Jay Groves (University of California, Berkeley, CA), and Michael Dustin (New York University, New York, NY).

The immunological synapse—the cell–cell junction between a T cell and antigen-presenting cell (APC)—looks like a bull's eye, with a central cluster of TCRs and their bound antigen–MHC ligands surrounded by a ring of adhesion molecules and their ligands. Active TCR clusters form at the periphery but then move toward the center, where they stop signaling.

To determine whether this change of locale is necessary for TCR shutdown, the group blocked the inward transport. They first replaced the APC with a supported lipid bilayer containing antigen–MHC and an adhesion ligand. They then etched chromium barriers onto the substrate to form variously patterned corrals within which MHC-bound TCRs would be trapped.

TCRs that were stuck in peripheral corrals signaled longer, as measured by their phosphorylation status and ability to elevate cytoplasmic calcium levels. "It's not just a matter of timing," says Dustin. "Location of the TCR clusters is important." It is not clear whether the periphery is a particularly good environment to sustain signaling, the center is a particularly good environment to kill signaling, or both. Positive feedback from dynamic actin in the periphery or negative feedback from centrally located inhibitors, perhaps phosphatases, might be involved.

The group artificially prevented TCR transport, but certain APCs, such as dendritic cells, might have that innate ability. Compared with B cells, dendritic cells are much more potent T cell activators. "So," Dustin wonders, "do they have their own version of these barriers?" Perhaps yes, as at least one report suggested that dendritic cells cause T cells to cluster TCRs in multiple peripheral foci rather than at the typical bull's eye of a B cell.

Reference:

Mossman, K.D., et al. 2005. Science. 310:1191–1193.[Abstract/Free Full Text]

Rabiya S. Tuma

rabiya{at}nasw.org

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This Article Full Text (PDF, 355K) 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 Tuma, R. S. Search for Related Content PubMed Articles by Tuma, R. S. Social Bookmarking                            What's this?