The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families

被引:142
作者
Park, SH [1 ]
Weiss, A
Benlagha, K
Kyin, T
Teyton, L
Bendelac, A
机构
[1] Korea Univ, Grad Sch Biotechnol BK21, Dept Biol, Seoul 136701, South Korea
[2] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
[3] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
关键词
CD1; TCR; autoreactivity; T cell development; lipid antigens;
D O I
10.1084/jem.193.8.893
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 nice, 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/alpha -galactosylceramide, which specifically identify the previously described CD1d autoreactive V alpha 14-J alpha 18/V beta8 natural killer (NK) T cells. Furthermore, zooming in on the CD1d-dependent non-V alpha 14 T cells, we found that, like V alpha 14 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, gamma delta 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.
引用
收藏
页码:893 / 904
页数:12
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