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

NKT cells m 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 m the context of CD 1 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 (mCII(707-721)), was not associated with either MHC class I or II Activation of CD1d-restricted mCII(707-721)-specific NKT cells was induced via TCR signaling and classical costimulation hi addition, mCII(707-721)-specific NKT cells induced T cell death through Fas/FasL, man IL-17A-independent fashion Moreover, mCII(707-721)-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 mCII(707) (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 disease