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Int Immunol. 2006 Nov;18(11):1615-25. Epub 2006 Sep 27.

Analyses of TCR clustering at the T cell-antigen-presenting cell interface and its impact on the activation of naive CD4+ T cells.

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Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093, USA.


The role of micrometer-scale clustering of TCRs at the T cell-antigen-presenting cell (APC) interface in T cell activation is an area of active investigation. Here we have investigated the impact of variations in the extent of TCR clustering on the activation of naive CD4+ T cells. These T cells are derived from transgenic (tg) mice expressing TCRs (172.10 and 1934.4) specific for the N-terminal nonapeptide of MBP bound to I-A(u), and are associated with murine experimental autoimmune encephalomyelitis (EAE). The 172.10 TCR has a approximately 4-fold higher affinity for antigen relative to the 1934.4 TCR, allowing us to compare the properties of two tg T cells of different avidities. We observe that variations in large-scale TCR clustering at the T cell-APC interface do not correlate well with the extent of activation (CD25 or CD69 up-regulation and IL-2 or IFN-gamma production). Efficient activation can also be achieved in the absence of micrometer-scale TCR clustering, indicating that this is not a prerequisite for the effective stimulation of naive T cells.

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