Journal
JOURNAL OF IMMUNOLOGY
Volume 193, Issue 1, Pages 56-67Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1400315
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Funding
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
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TCR-dependent signaling events have been observed to occur in TCR microclusters. We found that some TCR microclusters are present in unstimulated murine T cells, indicating that the mechanisms leading to microcluster formation do not require ligand binding. These pre-existing microclusters increase in absolute number following engagement by low-potency ligands. This increase is accompanied by an increase in cell spreading, with the result that the density of TCR microclusters on the surface of the T cell is not a strong function of ligand potency. In characterizing their composition, we observed a constant number of TCRs in a microcluster, constitutive exclusion of the phosphatase CD45, and preassociation with the signaling adapters linker for activation of T cells and growth factor receptor-bound protein 2. The existence of TCR microclusters prior to ligand binding in a state that is conducive for the initiation of downstream signaling could explain, in part, the rapid kinetics with which TCR signal transduction occurs.
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