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A Profound Alteration of Blood TCRB Repertoire Allows Prediction of Cerebral Malaria¹

Alexis Collette^2,*,, Sébastien Bagot^*,, Maria E. Ferrandiz^*, Pierre-André Cazenave^*, Adrien Six^3,* and Sylviane Pied^*,

^* Immunophysiopathologie Infectieuse, Centre National de la Recherche Scientifique Unité de Recherche Associée 1961, Institut Pasteur, and Université Pierre et Marie Curie, and Institut National de la Santé et de la Recherche Médicale Unité 511, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France

Cerebral malaria (CM) is one of the severe complications of Plasmodium infection. In murine models of CM, T cells have been implicated in the neuropathogenesis. To obtain insights into the TCRB repertoire during CM, we used high throughput CDR3 spectratyping and set up new methods and software tools to analyze data. We compared PBL and spleen repertoires of mice infected with Plasmodium berghei ANKA that developed CM (CM⁺) or not (CM^–) to evidence modifications of the TCRB repertoire associated with neuropathology. Using distinct statistical multivariate methods, the PBL repertoires of CM⁺ mice were found to be specifically altered. This alteration is partly due to recurrently expanded T cell clones. Strikingly, alteration of the PBL repertoire can be used to distinguish between CM⁺ and CM^–. This study provides the first ex vivo demonstration of modifications of T cell compartment during CM. Finally, our original approach for deciphering lymphocyte repertoires can be transposed to various pathological conditions.

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