Journal
IMMUNITY
Volume 29, Issue 4, Pages 589-601Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2008.08.011
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- New Energy Development Organization
- NIH [AI043542, AI044931]
- Grants-in-Aid for Scientific Research [20114004] Funding Source: KAKEN
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T cell activation is mediated by microclusters; (MCs) containing T cell receptors (TCRs), kinases, and adaptors. Although TCR MCs translocate to form a central supramolecular activation cluster (cSMAC) of the immunological synapse at the interface of a T cell and an antigen- presenting cell, the role of MC translocation in T cell signaling remains unclear. Here, we found that the accumulation of MCs at cSMAC was important for T cell costimulation. Costimulatory receptor CD28 was initially recruited coordinately with TCR to MCs, and its signals were mediated through the assembly with the kinase PKC theta. The accumulation of MCs at the cSMAC was accompanied by the segregation of CD28 from the TCR, which resulted in the translocation of both CD28 and PKC theta to a spatially unique subregion of cSMAC. Thus, costimulation is mediated by the generation of a unique costimulatory compartment in the cSMAC via the dynamic regulation of MC translocation.
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