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© Research
Publication : PloS one

A TCRβ Repertoire Signature Can Predict Experimental Cerebral Malaria

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PloS one - 04 Feb 2016

Mariotti-Ferrandiz E, Pham HP, Dulauroy S, Gorgette O, Klatzmann D, Cazenave PA, Pied S, Six A

Link to Pubmed [PMID] – 26844551

PLoS ONE 2016;11(2):e0147871

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.

https://www.ncbi.nlm.nih.gov/pubmed/26844551