An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation

Bénédicte Manoury, Eric W. Hewitt, Nick Morrice, Pam M. Dando, Alan J. Barrett and Colin Watts ()
Additional contact information
Bénédicte Manoury: Wellcome Sciences Building, University of Dundee
Eric W. Hewitt: Wellcome Sciences Building, University of Dundee
Nick Morrice: MRC Protein Phosphorylation Unit, University of Dundee
Pam M. Dando: Medical Research Council Peptidase Laboratory, The Babraham Institute
Alan J. Barrett: Medical Research Council Peptidase Laboratory, The Babraham Institute
Colin Watts: Wellcome Sciences Building, University of Dundee

Nature, 1998, vol. 396, issue 6712, 695-699

Abstract: Abstract Foreign protein antigens must be broken down within endosomes or lysosomes to generate suitable peptides that will form complexes with class II major histocompatibility complex molecules for presentation to T cells. However, it is not known which proteases are required for antigen processing. To investigate this, we exposed a domain of the microbial tetanus toxin antigen (TTCF) to disrupted lysosomes that had been purified from a human B-cell line. Here we show that the dominant processing activity is not one of the known lysosomal cathepsins, which are generally believed to be the principal enzymes involved in antigen processing, but is instead an asparagine-specific cysteine endopeptidase. This enzyme seems similar or identical to a mammalian homologue1 of the legumain/haemoglobinase asparaginyl endopeptidases found originally in plants2 and parasites3. We designed competitive peptide inhibitors of B-cell asparaginyl endopeptidase (AEP) that specifically block its proteolytic activity and inhibit processing of TTCF in vitro. In vivo, these inhibitors slow TTCF presentation to T cells, whereas preprocessing of TTCF with AEP accelerates its presentation, indicating that this enzyme performs a key step in TTCF processing. We also show that N-glycosylation of asparagine residues blocks AEP action in vitro. This indicates that N-glycosylation could eliminate sites of processing by AEP in mammalian proteins, allowing preferential processing of microbial antigens.

Date: 1998
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/25379 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:396:y:1998:i:6712:d:10.1038_25379

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/25379

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().