A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase.
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.
Département d'Immunologie, CNRS URA 1960, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, France.
B
B
Reina-San-Martín
W
W
Degrave
C
C
Rougeot
A
A
Cosson
N
N
Chamond
A
A
Cordeiro-Da-Silva
M
M
Arala-Chaves
A
A
Coutinho
P
P
Minoprio
D000591:Amino Acid Isomerases / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D017125:Genes, Protozoan; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008934:Mitogens / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D008970:Molecular Weight; D017386:Sequence Homology, Amino Acid; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000276:immunology* / Q000472:pathogenicity
D017931:DNA Primers; D008934:Mitogens; D000591:Amino Acid Isomerases; C022451:proline racemase