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Original Article |
sehopark{at}korea.ac.kr
To define the phenotype and T cell receptor (TCR) repertoire of CD1d-dependent T cells, we compared the populations of T cells that persisted in major histocompatibility complex (MHC)-deficient mice, which lack mainstream T cells, with those from MHC/CD1d doubly deficient mice, which lack both mainstream and CD1d-dependent T cells. Surprisingly, up to 80% of the CD1d-dependent T cells were stained by tetramers of CD1d/
-galactosylceramide, which specifically identify the previously described CD1d autoreactive V14-J18/Vβ8 natural killer (NK) T cells. Furthermore, zooming in on the CD1d-dependent non-V14 T cells, we found that, like V14 NK T cells, they mainly expressed recurrent, CD1d autoreactive TCR families and had a natural memory phenotype. Thus, CD1d-restricted T cells differ profoundly from MHC-peptide–specific T cells by their predominant use of autoreactive and semiinvariant, rather than naive and diverse, TCRs. They more closely resemble other lineages of innate lymphocytes such as B-1 B cells, 
T cells, and NK cells, which express invariant or semiinvariant autoreactive receptors. Finally, we demonstrate that the MHC-restricted TCR repertoire is essentially non–cross-reactive to CD1d. Altogether, these findings imply that lipid recognition by CD1d-restricted T cells may have largely evolved as an innate rather than an adaptive arm of the mouse immune system.
Key Words: CD1 • TCR • autoreactivity • T cell development • lipid antigens
GalCer, -galactosylceramide; DN, double negative; TAP, transporter associated with antigen processing. S.-H. Park and A. Weiss contributed equally to this work.
© 2001 The Rockefeller University Press
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