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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. 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