title: A TCRβ Repertoire Signature Can Predict Experimental Cerebral Malaria.
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.
authors: Sorbonne Universités, UPMC Univ Paris 06, URA 1961 CNRS, F-75005, Paris, France.|CNRS, URA 1961 CNRS, F-75005, Paris, France.|Institut Pasteur, Immunophysiopathologie infectieuse, F-75015, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, UPMC Immunology- Immunopathology-Immunotherapy, F-75013, Paris, France.|Inserm, U959, Immunology-Immunopathology-Immunotherapy, F-75013, Paris, France.
authors: Encarnita
authors: E
authors: Mariotti-Ferrandiz
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, UPMC Immunology- Immunopathology-Immunotherapy, F-75013, Paris, France.|Inserm, U959, Immunology-Immunopathology-Immunotherapy, F-75013, Paris, France.
authors: Hang-Phuong
authors: HP
authors: Pham
authors: Sorbonne Universités, UPMC Univ Paris 06, URA 1961 CNRS, F-75005, Paris, France.|CNRS, URA 1961 CNRS, F-75005, Paris, France.|Institut Pasteur, Immunophysiopathologie infectieuse, F-75015, Paris, France.
authors: Sophie
authors: S
authors: Dulauroy
authors: Sorbonne Universités, UPMC Univ Paris 06, URA 1961 CNRS, F-75005, Paris, France.|CNRS, URA 1961 CNRS, F-75005, Paris, France.|Institut Pasteur, Immunophysiopathologie infectieuse, F-75015, Paris, France.
authors: Olivier
authors: O
authors: Gorgette
authors: Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, UPMC Immunology- Immunopathology-Immunotherapy, F-75013, Paris, France.|Inserm, U959, Immunology-Immunopathology-Immunotherapy, F-75013, Paris, France.
authors: David
authors: D
authors: Klatzmann
authors: Sorbonne Universités, UPMC Univ Paris 06, URA 1961 CNRS, F-75005, Paris, France.|CNRS, URA 1961 CNRS, F-75005, Paris, France.|Institut Pasteur, Immunophysiopathologie infectieuse, F-75015, Paris, France.
authors: Pierre-André
authors: PA
authors: Cazenave
authors: Sorbonne Universités, UPMC Univ Paris 06, URA 1961 CNRS, F-75005, Paris, France.|CNRS, URA 1961 CNRS, F-75005, Paris, France.|Institut Pasteur, Immunophysiopathologie infectieuse, F-75015, Paris, France.
authors: Sylviane
authors: S
authors: Pied
authors: Sorbonne Universités, UPMC Univ Paris 06, URA 1961 CNRS, F-75005, Paris, France.|CNRS, URA 1961 CNRS, F-75005, Paris, France.|Institut Pasteur, Immunophysiopathologie infectieuse, F-75015, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, UPMC Immunology- Immunopathology-Immunotherapy, F-75013, Paris, France.|Inserm, U959, Immunology-Immunopathology-Immunotherapy, F-75013, Paris, France.
authors: Adrien
authors: A
authors: Six
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000469:parasitology; D022801:Complementarity Determining Regions / Q000235:genetics; D004195:Disease Models, Animal; D014644:Genetic Variation; D016779:Malaria, Cerebral / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D010962:Plasmodium berghei; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta