Natural Killer T (NKT) cells are distinct lymphocyte lineages that recognize lipid antigens presented by the non-classical Major Histocompatibility Complex molecule CD1d. Two categories of NKT cells, type I and type II, have been described based on T-cell receptor expression and antigenic specificity. In both cases, increasing evidence suggest that recognition of self-antigens by these cells plays an important role not only in their development but also in their regulation of a broad range of immune responses. Here we review recent advances in our understanding of how and when NKT cell autoreactivity manifests itself, how the NKT T cell receptor engages self-antigens and the nature of these self-antigens.
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