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.
Reina-San-Martín
B
B
Département d'Immunologie, CNRS URA 1960, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, France.
Degrave
W
W
Rougeot
C
C
Cosson
A
A
Chamond
N
N
Cordeiro-Da-Silva
A
A
Arala-Chaves
M
M
Coutinho
A
A
Minoprio
P
P
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