NKT cells are associated with immunological control of autoimmune disease a
nd cancer and can recognize cell surface mCD1d without addition of exogenou
s antigens. Cellular antigens presented by mCD1d have not been identified,
although NKT cells can recognize a synthetic glycolipid, alpha-GalCer. Here
we show that after addition of a lipid extract from a tumor cell line, pla
te-bound mCD1d molecules stimulated an NKT cell hybridoma. This hybridoma a
lso responded strongly to three purified phospholipids, but failed to recog
nize alpha-GalCer. Seven of sixteen other mCD1d restricted hybridomas also
showed a response to certain purified phospholipids. These findings suggest
NKT cells can recognize cellular antigens distinct from alpha-GalCer and i
dentify phospholipids as potential self-antigens presented by mCD1d.