Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice

Neuroinflammation Unit, Biotech Research and Innovation Centre, University of Copenhagen, Denmark.
The Journal of clinical investigation (Impact Factor: 13.22). 01/2011; 121(1):249-64. DOI: 10.1172/JCI43964
Source: PubMed


NKT cells in the mouse recognize antigen in the context of the MHC class I-like molecule CD1d and play an important role in peripheral tolerance and protection against autoimmune and other diseases. NKT cells are usually activated by CD1d-presented lipid antigens. However, peptide recognition in the context of CD1 has also been documented, although no self-peptide ligands have been reported to date. Here, we have identified an endogenous peptide that is presented by CD1d to activate mouse NKT cells. This peptide, the immunodominant epitope from mouse collagen type II (mCII707-721), was not associated with either MHC class I or II. Activation of CD1d-restricted mCII707-721-specific NKT cells was induced via TCR signaling and classical costimulation. In addition, mCII707-721-specific NKT cells induced T cell death through Fas/FasL, in an IL-17A-independent fashion. Moreover, mCII707-721-specific NKT cells suppressed a range of in vivo inflammatory conditions, including delayed-type hypersensitivity, antigen-induced airway inflammation, collagen-induced arthritis, and EAE, which were all ameliorated by mCII707-721 vaccination. The findings presented here offer new insight into the intrinsic roles of NKT cells in health and disease. Given the results, endogenous collagen peptide activators of NKT cells may offer promise as novel therapeutics in tissue-specific autoimmune and inflammatory diseases.

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Available from: Saleh M Ibrahim
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    • "NKT cells are a subgroup of T-cells, which express the NK cell surface marker NK1.1 and a restricted TCR repertoire recognizing glycolipids and self-peptides presented by the major histocompatibility complex class 1-related glycoprotein CD1d (Fowlkes et al., 1987; Makino et al., 1995; Issazadeh-Navikas, 2012; Liu et al., 2011a). Besides being expressed on professional APCs a recent report has shown that CD1d is also expressed on epithelial cells in the human vagina (Kawana et al., 2008). "
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    • "SGL-S23 also suppressed histamine release, and more effectively so than α-GalCer or high dose IFN-γ. Finally, CIA suppression through NKT cell manipulation can be accomplished with nonglycolipid stimulation as shown by Liu et al. (2011). Immunisation with murine CII induces a weaker responsethan heterologous collagen, characterised by multiple epitopes sharing a common motif, the strongest located at position 707-721. "

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