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

Pastor, Silvia, Vaccaro, Carlos G., Minguela, Alfredo, Ober, Raimund J. and Ward, E. Sally (2006) Analyses of TCR clustering at the T cell-antigen-presenting cell interface and its impact on the activation of naive CD4⁺ T cells. International Immunology, 18 (11), 1615-1625. (doi:10.1093/intimm/dxl095).

Abstract

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 ∼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-γ 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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Contributors

Author: Raimund J. Ober

Author: E. Sally Ward

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