Group 1 CD1-restricted T cells take center stage.

The recognition of lipid antigens by T cells is a complex and fascinating phenomenon. The MHC-like molecules of the CD1 family have evolved to present a wide variety of both self and foreign lipids for recognition by T-cell receptors. While much progress has been made in our understanding of the NKT cells that recognize lipids presented by CD1d molecules, our knowledge of the T-cell populations directed at the related group 1 CD1 molecules, i.e. CD1a, CD1b and CD1c, has lagged behind. In this issue of the European Journal of Immunology, a study identifies a surprisingly large portion of human peripheral blood T cells as being autoreactive to the group 1 CD1 proteins. This work and other recent developments highlight the presence of a substantial number of unconventional T cells as part of our normal T-cell repertoire. This interesting finding is discussed in details in this commentary.