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Original Article |
Correspondence to: Se-Ho Park, Dept. of Biology, BK21 Graduate School of Biotechnology, Korea University, Seoul 136-701, South Korea. Tel:82-2-3290-3160 Fax:82-2-923-9522 E-mail: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/Vß8 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
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