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

Int Immunol. 2006 Nov;18(11):1615-25. doi: 10.1093/intimm/dxl095. Epub 2006 Sep 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Down-Regulation / immunology
  • Lymphocyte Activation*
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / physiology*


  • Receptors, Antigen, T-Cell