International Immunology Advance Access published online on April 13, 2004
International Immunology, doi:10.1093/intimm/dxh079
© 2004 by The Japanese Society for Immunology
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1 Department of Clinical Chemistry, Lund University, 221 84 Lund, Sweden; Department of Medical Inflammation Research, Lund University, 221 84 Lund, Sweden
* To whom correspondence should be addressed. E-mail: Meirav.Holmdahl{at}inflam.lu.se.
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. Keywords:
Keywords: antigen degradation, immune dominant CII peptide, MHC class II, mouse, protease inhibition
Accepted February 16, 2004
Article
Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells
2 Department of Clinical Chemistry, Lund University, 221 84 Lund, Sweden
3 Department of Medical Inflammation Research, Lund University, 221 84 Lund, Sweden
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