The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families
The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families
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DOI：
10.1084/jem.193.8.893
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发表时间：
2001-04-16
影响因子：
15.3
通讯作者：
Bendelac, A
中科院分区：
文献类型：
--
作者：
Park, SH;Weiss, A;Bendelac, A
为了确定CD 1d依赖性T细胞的表型和T细胞受体（TCR）库，我们比较了主要组织相容性复合体（MHC）缺陷型小鼠（缺乏主流T细胞）中持续存在的T细胞群，以及MHC/CD 1d双缺陷型小鼠（缺乏主流和CD 1d依赖性T细胞）中的T细胞群。令人惊讶的是，高达80%的CD 1d依赖性T细胞被CD 1d/α-半乳糖神经酰胺的四聚体染色，其特异性地识别先前描述的CD 1d自身反应性V α 14-J α 18/V β 8自然杀伤（NK）T细胞。此外，放大CD 1d依赖性非V α 14 T细胞，我们发现，与V α 14 NK T细胞一样，它们主要表达复发性、CD 1d自身反应性TCR家族，并具有自然记忆表型。因此，CD 1d限制性T细胞与MHC肽特异性T细胞的显著不同之处在于它们主要使用自身反应性和半不变的TCR，而不是幼稚和多样的TCR。它们更类似于先天淋巴细胞的其他谱系，如B-1 B细胞、γ δ T细胞和NK细胞，这些细胞表达不变或半不变的自身反应性受体。最后，我们证明了MHC限制性TCR库基本上与CD 1d无交叉反应。总而言之，这些发现意味着CD 1d限制性T细胞的脂质识别可能在很大程度上是作为小鼠免疫系统的先天而非适应性臂进化的。
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.