Voie d'immunisation et séquence d'administration de l ... - TEL

tel-00827710, version 1 - 29 May 2013
into one of two types of endosomes that can mature with different kinetics: one population
matures rapidly, favoring acidification, antigen degradation and presentation on MHC-II,
whereas the other group is characterized by more stable pH and enzymatic activity, leading to
more efficient cross-presentation on MHC-I. For example, antigens that are endocytosed
through mannose receptor are directed to the stable endosomes and result in cross-
presentation, whereas the endocytosis through scavenger receptors, DC-SIGN, or pinocytosis
targets antigen to the acidic endosome compartment and results in presentation on MHC-II
(Burgdorf et al., 2007). Some receptors such as DEC-205 have the ability to promote both
MHC-I and MHC-II presentations (Mahnke et al., 2000; Dudziak et al., 2007).
3) DC activation
In the steady state, DCs are immature, displaying a high ability for phagocytosis, and high
levels of surface expression of a large pattern of engulfment receptors, but a low capacity to
activate naïve T cells (Wilson et al., 2003). During antigen processing and presentation, the
phenotype of DCs matures, also dependent on the other signals they have received (Steinman,
2003). Signals helping DCs to distinguish what is ‘self’ and ‘non-self’ are particularly critical
to allow their maturation and the development of an appropriate response. In inflammatory
conditions, these cells mature and acquire a phenotype allowing for the activation of antigen-
specific T cells. While immature DCs have a strong capacity for phagocytosis and a low
expression of MHC-II molecules on their surface, these two characteristics are inverted
during maturation, with a severe decrease in phagocytosis capacity and an increase in the
MHC-II surface expression observed. In parallel, DCs increase their expression of
costimulatory molecules and cytokines required for T cell activation. Moreover, the maturing
migratory DCs upregulate the expression of the chemokine receptor CCR7, allowing for
interaction with the gradient of chemokines CCL19 and CCL21 released by cells from the
stroma and high endothelial veinules in the lymph nodes. At this point, the DCs modify their
morphology and migrate to lymphoid organs where they will interact with T cells (Verdijk et
al., 2004) (Figure 4).
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