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Article Dans Une Revue PLoS ONE Année : 2016

A TCRβ Repertoire Signature Can Predict Experimental Cerebral Malaria

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Cerebral Malaria (CM) is associated with a pathogenic T cell response. Mice infected by P. berghei ANKA clone 1.49 (PbA) developing CM (CM +) present an altered PBL TCR repertoire, partly due to recurrently expanded T cell clones, as compared to non-infected and CM-infected mice. To analyse the relationship between repertoire alteration and CM, we performed a kinetic analysis of the TRBV repertoire during the course of the infection until CM-related death in PbA-infected mice. The repertoires of PBL, splenocytes and brain lympho-cytes were compared between infected and non-infected mice using a high-throughput CDR3 spectratyping method. We observed a modification of the whole TCR repertoire in the spleen and blood of infected mice, from the fifth and the sixth day post-infection, respectively, while only three TRBV were significantly perturbed in the brain of infected mice. Using multivariate analysis and statistical modelling, we identified a unique TCRβ signature discriminating CM + from CTR mice, enriched during the course of the infection in the spleen and the blood and predicting CM onset. These results highlight a dynamic modification and compartmentaliza-tion of the TCR diversity during the course of PbA infection, and provide a novel method to identify disease-associated TCRβ signature as diagnostic and prognostic biomarkers.
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hal-01284361 , version 1 (07-03-2016)

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Encarnita Mariotti-Ferrandiz, Hang-Phuong Pham, Sophie Dulauroy, Olivier Gorgette, David Klatzmann, et al.. A TCRβ Repertoire Signature Can Predict Experimental Cerebral Malaria. PLoS ONE, 2016, 11 (2), pp.e0147871. ⟨10.1371/journal.pone.0147871⟩. ⟨hal-01284361⟩
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