A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase

Author:  ["Bernardo Reina-San-Martín","Wim Degrave","Catherine Rougeot","Alain Cosson","Nathalie Chamond","Anabela Cordeiro-da-Silva","Mario Arala-Chaves","Antonio Coutinho","Paola Minoprio"]

Publication:  Nature Medicine

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Tags:     Medicine

Abstract

Lymphocyte polyclonal activation is a generalized mechanism of immune evasion among pathogens. In a mouse model of Trypanosoma cruzi infection (American trypanosomiasis), reduced levels of polyclonal lymphocyte responses correlate with resistance to infection and cardiopathy. We report here the characterization of a parasite protein with B-cell mitogenic properties in culture supernatants of infective forms, the cloning of the corresponding gene and the analysis of the biological properties of its product. We characterized the protein as a co-factor-independent proline racemase, and show that its expression as a cytoplasmic and/or membrane-associated protein is life-stage specific. Inhibition studies indicate that availability of the racemase active site is necessary for mitogenic activity. This is the first report to our knowledge of a eukaryotic amino acid racemase gene. Our findings have potential consequences for the development of new immune therapies and drug design against pathogens.

Cite this article

Reina-San-Martín, B., Degrave, W., Rougeot, C. et al. A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase. Nat Med 6, 890–897 (2000). https://doi.org/10.1038/78651

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