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

Lymphocyte polyclonal activation is a generalized mechanism of immune evasi on among pathogens. In a mouse model of Trypanosoma cruzi infection (Americ an trypanosomiasis), reduced levels of polyclonal lymphocyte responses corr elate with resistance to infection and cardiopathy. We report here the char acterization of a parasite protein with B-cell mitogenic properties in cult ure supernatants of infective forms, the cloning of the corresponding gene and the analysis of the biological properties of its product. We characteri zed 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 racema se active site is necessary for mitogenic activity. This is the first repor t to our knowledge of a eukaryotic amino acid racemase gene. Our findings h ave potential consequences for the development of new immune therapies and drug design against pathogens.