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

tel-00827710, version 1 - 29 May 2013
C. Inhibition of cross-presentation with anti-K b -SIINFEKL
antibody
Given the differences we observed for the persistence of antigen upon i.d. or i.v.
immunization (Figures 32 and 33), we hypothesized that this may explain why we obtained
an enhanced T cell response after local antigen delivery. It was possible that i.d.
immunization resulted in a local antigen depot that would allow for the delayed release of
antigen from the site of injection and, consequently, an extended period of antigen
presentation in lymphoid organs and a better CD8 + T cell response. This model was also in
line with previous results obtained in our lab showing that persistence of antigen is required to
have effective cross-priming (Jusforgues-Saklani et al., 2008).
To test this hypothesis, we injected mice with antibodies directed against the MHC-I-peptide
complexe: H-2K b -SIINFEKL. In this way the antibody will bind and mask antigen, blocking
its presentation to T cells. This antibody has been previously characterized and used to block
antigen presentation in vivo (Obar and Lefrancois, 2010). If our hypothesis was true, we
expected to obtain the same level of response for i.d.-immunized mice that were injected with
blocking antibody one week after immunization, and for i.v.-immunized animals. Yet this was
not the result observed: the injection of the blocking antibody did not appear to impact the T
cell response at all (Figure 36A, B). From these data, it is unclear whether our hypothesis was
incorrect, or if the antibody is not efficient at blocking persistent cross-presentation. Indeed, it
is difficult to address this question and validate its effect on peptide presentation, as it does
not block OT-I proliferation in a control experiment (Figure 36C). Another strategy could be
used to address this question: the injection of diphteria toxin receptor-expressing splenocytes
could be performed, followed by their removal upon treatment with diphteria toxin. The
ability to manipulate the presence of the antigen depot would allow for the investigation of
the impact of antigen persistence on T cell priming over time.
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