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International Immunology Advance Access published online on September 27, 2006
International Immunology, doi:10.1093/intimm/dxl095
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received January 10, 2006
Accepted August 27, 2006

Article

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

Silvia Pastor 1, Carlos G. Vaccaro 1, Alfredo Minguela 2, Raimund J. Ober 3, and E. Sally Ward 4 *

1 Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093, USA
2 Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093, USA; Immunology Service, University Hospital ‘Virgen de la Arrixaca’, El Palmer, Murcia, Spain
3 Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093, USA; Department of Electrical Engineering, University of Texas at Dallas, Richardson, TX 75080, USA
4 Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093, USA; Cancer Immunobiology Center, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-8576, USA

* To whom correspondence should be addressed.
E. Sally Ward, E-mail: sally.ward{at}utsouthwestern.edu


  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-Au, 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-{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.

Keywords: autoimmunity; experimental autoimmune encephalomyelitis; naive T cell activation; peptide-MHC class II.
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