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

tel-00827710, version 1 - 29 May 2013
a limited amount of transgenic cells must be transferred in order to interpret the data as a
mimic of the endogenous repertoire.
2) Recent improvement: tetramer-based enrichment
To overcome the problem of the low T cell frequency for a given specificity in the
endogenous repertoire, Moon and colleagues developed a new technique using tetramer-based
enrichment to detect rare CD4 + T cells of a given specificity (Moon et al., 2007). To use this
technique, the cells are first stained with MHC-I-peptide tetramers and then enriched, using
magnetic beads. In this way, it is possible to enrich tetramer-positive T cells more than 100-
fold. This strategy successfully managed to detect antigen-specific T cells in a naïve mouse
and has been adapted and optimized for the study of CD8 + T cells in vivo (Obar et al., 2008).
B. Conditions of immunization
As briefly introduced previously, the outcome of a T cell response may be regulated by the
conditions of immunization. The characteristics of the antigen, the administration methods,
and the inflammatory context in which the injection is performed are all parameters that could
modify the T cell response. These potential points of variation should be anticipated and
carefully considered when developing an experimental system in order to be as close as
possible to the physiologic and clinical conditions one is attempting to model.
1) Antigen form and dose
As described previously, different forms of antigen are used in vaccinology, as well as in
experimental animal models. The time needed to elicit an effector T cell response upon
antigen injection depends on several factors including the nature of antigen and/or the context
of immunization. For instance, antigen presentation occurs rapidly after the injection of 8-10
mer peptide vaccines because processing is not required. On the contrary, there is a
considerably longer delay when injecting a cell-associated antigen that has to be
phagocytosed and processed prior to presentation. Moreover, it is possible to target vaccines
to different DC subsets by complexing the antigen with specific antibodies such as DEC-205,
the administration of the vaccine in a specific location, or via its expression as part of viral
vectors that infects a particular cell type of interest. Knowing that DC subsets have different
abilities to present antigen on MHC-I or –II and, as a result, trigger various T cell or B cell
responses, the choices of antigen form and delivery technique/location are of major
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