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tel-00827710, version 1 - 29 May 2013
Figure 8. Three signals model for the activation of antigen-specific T cells by DCs.
1) Signal 1: interaction between the TCR and the peptide-MHC-I complex
The first signal required for T cell activation is the interaction between the peptide-MHC-I
complex at the DC surface and the TCR on an antigen-specific T cell. The density of peptide-
MHC complexes at the surface of DC and their affinity for the TCR both regulate the
outcome of the T cell activation. For instance, using a peptide with a better affinity in vitro
promotes the proliferation of specific T cells despite stimulating with a lower concentration of
antigen (Hemmer et al., 1998). Concerning the number of peptide-MHC complexes, it has
been shown that increasing the density of peptide-MHC complexes induces the proliferation
of high affinity, but also lower affinity T cells (Rees et al., 1999). Zehn and colleagues
developed an elegant model to study the impact of the T cell affinity for antigen on the T cell
response, using altered peptide ligands that bind equivalently the MHC molecule but have
differing abilities to interact with specific TCR-transgenic T cells (Zehn et al., 2009). They
showed that weak interactions are sufficient to activate naïve T cells but that strong
interaction is required to induce a sustained and robust T cell response. More recently, it has
been shown that TCR affinity for the peptide-MHC complex is critically important. By
comparing weak stimulations resulting from either a decreased antigen affinity or a decreased
density of peptide-MHC complexes, Gottschalk and colleagues demonstrated that, although
both induce T cell proliferation, the condition with the highest affinity induces a better
responsiveness of T cells to IL-2 and sustained interaction between DCs and T cells
(Gottschalk et al., 2012).
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