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

tel-00827710, version 1 - 29 May 2013
A. Naïve T cells: diversity of the repertoire
Mature CD8 + T lymphocytes bear T cell receptors (TCR) that are specific for a MCH class I
molecule bound to a unique peptide. This TCR is a heterodimer of αβ chains. Each gene is
composed of segments that were joined by somatic recombination during lymphocyte
development (Figure 7). The Vβ chain is composed of 3 different segments Vβ, Dβ and Jβ.
During the rearrangement process, nucleotides are randomly added or removed at junction
sites creating variability between different TCRβ chains. This region of high variability is
called CDR3 (Complementary-determining Region 3) and is thought to carry the specificity
for the specific epitope. The recombination of these 3 segments constitutes the variable region
and is associated with a constant region Cβ. The same mechanism is responsible for the
formation of α chain except that there is only recombination between two segments for the
variable region: Vα and Jα. Then the α and β chains associate to form the TCR. The random
variability created during somatic recombination is responsible for the high diversity of TCRs
present in an organism. Interestingly there is also extensive variability between the T cell
repertoire of different individuals (Bousso et al., 1998). In the endogenous repertoire of mice,
the number of T cells specific for a given antigen ranges from 10 to 1000 cells per individual
animal (Casrouge et al., 2000).
Figure 7. Somatic recombination leading to rearranged DNA coding for the TCRβ chain. Three
segments V, D and J are associated to constitute the variable part of the chain. Additional nucleotides
are removed or added at the junctions, introducing variability in the sequence.
B. T cell activation by dendritic cells
Naïve T cells are activated after following their encounter with an antigen-presenting cell in
the secondary lymphoid organs. Several signals are required for complete activation and
differentiation of the CD8 + T cells (Figure 8).
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