Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells.
Författare
Summary, in English
Development of type-II collagen (CII)-induced arthritis (CIA) is dependent on activation of CII-reactive T cells. Dendritic cells (DCs) are believed to play a crucial role in antigen-specific priming of T cells but it is still unclear how the CII-reactive T cells are primed since Langerhans cells (LCs) are poor antigen-presenting cells for CII. In the present study we show that LCs, treated with cysteine protease inhibitors, are able to process and present CII to T-cell hybridomas specific for the immune-dominant glycosylated 259–270 peptide bound to the MHC class II molecule Aq. Interestingly, the self (mouse) CII peptide could also now be efficiently presented. The poor presentation by LCs is a peptide-specific effect, since both bovine CII (bCII) (presenting a different peptide on H-2r) and ovalbumin could be efficiently presented, and blockage of cysteine proteases did not enhance antigen presentation. The enhanced CII-presentation by cysteine protease inhibition is seen mainly in LCs and not in antigen-primed B cells or macrophages. B cell and macrophage presentation of CII occur even without protease inhibition and are only to a minor extent influenced by cysteine protease inhibition. These data suggest that a LC deficiency in processing of the immune-dominant CII epitope in both CIA and RA may limit the exposure of this self-antigen to T cells, but that presentation can be overcome by modulation of the peptide proteolysis during CII processing.
Avdelning/ar
Publiceringsår
2004
Språk
Engelska
Sidor
717-726
Publikation/Tidskrift/Serie
International Immunology
Volym
16
Issue
5
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Immunology in the medical area
Status
Published
Forskningsgrupp
- Immunology
ISBN/ISSN/Övrigt
- ISSN: 1460-2377