In addition to its well-established role in innate immunity, the complement component C3 is of critical importance in modulating the humoral response. In this study, we examined the effect of C3b linkage to tetanus toxin (TeNT) in the production of antigenic peptides inside human APC. We purified HLA-DR associated peptides isolated either from TeNT or TeNT-C3b pulsed cells. This study revealed that TeNT-C3b derived antigenic peptides are different and more numerous than TeNT derived peptides. This increased production of antigenic peptides correlated with a C3b-induced TeNT modification of proteolysis. These findings argue in favour of a new role for C3b in the modulation of T cell epitope during antigen processing and presentation.