A TCRβ Repertoire Signature Can Predict Experimental Cerebral Malaria

Encarnita Mariotti-Ferrandiz, Hang-Phuong Pham, Sophie Dulauroy, Olivier Gorgette, David Klatzmann, Pierre-André Cazenave, Sylviane Pied and Adrien Six

PLOS ONE, 2016, vol. 11, issue 2, 1-17

Abstract: 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 lymphocytes 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 compartmentalization 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0147871

DOI: 10.1371/journal.pone.0147871

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