Many important biological cascades are tightly regulated via protein-protein interactions. Interactions of TM, known to be a regulator of blood clotting, with the complement system, an important part of innate immunity, could play an important role in a link between the coagulation cascade and the inflammatory response. A pull-down assay using an immobilized lectin-like domain of TM showed that there is an interaction between this domain and complement component C3. Studies are currently underway to better characterize this interaction to elucidate the role that TM may play in the complement system. The lectin-like domain of TM has been expressed in and purified from the yeast, Pichia pastoris. Complement component C3 has been isolated from plasma, purified and activated to C3b. Analysis by SDS-PAGE and mass spectrometry verified that both of the desired proteins were isolated. Both proteins were then subjected to digestion with pepsin at low pH to determine their suitability for study by hydrogen/deuterium (H/D) exchange and mass spectrometry (MS). Peptide coverage maps of each protein are being prepared. The H/D exchange of the individual proteins will be analyzed by MALDI-TOF MS. The interactions between TM and C3/C3b will then also be investigated by H/D exchange and MS among other methods.