Beschreibung:
<jats:p>Trypanosomes encode a family of proteins known as Major Surface Metalloproteases (MSPs). We have identified six putative MSPs encoded within the partially sequenced<jats:italic>T. congolense</jats:italic>genome. Phylogenic analysis indicates that<jats:italic>T. congolense</jats:italic>MSPs belong to five subfamilies that are conserved among African trypanosome species. Molecular modeling, based on the known structure of<jats:italic>Leishmania Major</jats:italic>GP63, reveals subfamily-specific structural variations around the putative active site despite conservation of overall structure, suggesting that each MSP subfamily has evolved to recognize distinct substrates. We have cloned and purified a protein encoding the amino-terminal domain of the<jats:italic>T. congolense</jats:italic>homologue TcoMSP-D (most closely related to<jats:italic>Leishmania</jats:italic>GP63). We detect TcoMSP-D in the serum of<jats:italic>T. congolense</jats:italic>-infected mice. Mice immunized with the amino-terminal domain of TcoMSP-D generate a persisting IgG1 antibody response. Surprisingly, a low-dose challenge of immunized mice with<jats:italic>T. congolense</jats:italic>significantly increases susceptibility to infection, indicating that immunity to TcoMSP-D is a factor affecting virulence.</jats:p>