Antigen cross-presentation by dendritic cells (DC) is an enigmatic process essential for viral and anti-tumour immunity, and for suppression of autoimmunity. New evidence from our group using a mouse model suggests that the intracellular protease inhibitor Serpinb9 regulates an unidentified DC protease involved in cross-presentation. The serpin-protease interaction does not affect initial antigen processing or transfer into the cytoplasm. It likely has a key role in the cytoplasm, influencing eventual display of antigens at the DC surface. Here we propose to (1) Identify and characterize the target protease in DC (2) Determine the importance of Serpinb9 to DC function in tissues (3) Examine Serpinb9 expression by cross-presenting human DC.