The My(c)stery of iNKT cell ontogeny

Invariant Vα14 bearing natural killer T cells (iNKT) cells constitute a subset of lymphocytes that recognize lipid-based ligands presented by the non-classical MHC class I-like molecule CD1d and responds with rapid cytokine production. Despite their multiple implications in regulating immune responses, pertaining to cancer and auto-immunity, the molecular requirements for their development in the thymus are poorly understood. Here we discuss recent evidence that c-Myc mediates an intrathymic proliferation wave immediately following agonist selection of iNKT cells that is vital for the generation of mature iNKT cells in vivo. We review aspects of early iNKT ontogeny in light of our findings and speculate about possible mechanistic links controlling c-Myc activity in newly selected cells.