Abstract:
The mammalian legumain, also called asparaginyl endopeptidase
(AEP), is critically involved in the processing
of bacterial antigens for MHC class II presentation.
In order to investigate the substrate specificity
of AEP in the P1’ position, we created a peptide library
and digested it with purified pig kidney AEP. Digestion
was less efficient only when proline was in
the P1’ position. Maximum AEP activity was found in
lysosomal fractions of different types of antigen presenting
cells (APC). When the multiple sclerosis-associated
autoantigen myelin basic protein (MBP) was
digested with AEP, the immunodominant epitope
83 – 99 was destroyed. Myoglobin as an alternative
substrate was AEP resistant. These results suggest
an important, but not necessarily critical role for AEP
in lysosomal antigen degradation