International Immunology Advance Access originally published online on April 13, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
International Immunology, Vol. 16, No. 5, pp. 717-726,
May 2004
© 2004 Japanese Society for Immunology
Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells
1 Department of Clinical Chemistry, Lund University and 2 Department of Medical Inflammation Research, Lund University, 221 84 Lund, Sweden
Correspondence to: M. Holmdahl; E-mail: Meirav.Holmdahl@inflam.lu.se
Transmitting editor: G. J. Hammerlin
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: antigen degradation, immune dominant CII peptide, MHC class II, mouse, protease inhibition
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. von Delwig, D. M Altmann, F. G Charlton, N. McKie, J. D Isaacs, R. Holmdahl, and J. H Robinson T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice Ann Rheum Dis, May 1, 2007; 66(5): 599 - 604. [Abstract] [Full Text] [PDF]
|
|