Forestier Claire, Park Se-Ho, Wei Datsen, Benlagha Kamel, Teyton Luc, Bendelac Albert
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
J Immunol. 2003 Oct 15;171(8):4096-104. doi: 10.4049/jimmunol.171.8.4096.
CD1d and nonclassical MHC molecules differ markedly from classical MHC ligands in their ability to promote the selection and differentiation of developing T cells. Whereas classical MHC-restricted T cells have a predominantly naive phenotype and a broad TCR repertoire, most other T cells have a memory and/or NKT phenotype with a restricted repertoire. Because the nonclassical ligands selecting these memory-type cells are expressed by bone marrow-derived cells, it has been suggested that the development of large repertoires of naive-type cells was dependent on the classical MHC expression pattern in the thymus cortex, high on epithelial cells and low on cortical thymocytes. We redirected CD1d expression using the classical MHC II Ealpha promoter. pEalpha-CD1d mice lacked memory-type NKT cells, but, surprisingly, they did not acquire the reciprocal ability to select a diverse population of naive CD1d-restricted cells. These findings suggest that, whereas the development of NKT cells is dependent on the pattern of CD1d expression, the absence of a broad, naive CD1d-restricted T cell repertoire may reflect intrinsic limitations of the pool of TCR genes or lipid Ags.
CD1d和非经典MHC分子在促进发育中T细胞的选择和分化能力方面与经典MHC配体有显著差异。经典MHC限制性T细胞主要具有幼稚表型和广泛的TCR库，而大多数其他T细胞具有记忆和/或NKT表型且库受限。由于选择这些记忆型细胞的非经典配体由骨髓来源的细胞表达，因此有人提出，幼稚型细胞的大量库的发育依赖于胸腺皮质中经典MHC的表达模式，在上皮细胞上高表达而在皮质胸腺细胞上低表达。我们使用经典MHC II Eα启动子重定向CD1d表达。pEα-CD1d小鼠缺乏记忆型NKT细胞，但令人惊讶的是，它们没有获得选择多样化幼稚CD1d限制性细胞群体的相应能力。这些发现表明，虽然NKT细胞的发育依赖于CD1d表达模式，但缺乏广泛的幼稚CD1d限制性T细胞库可能反映了TCR基因库或脂质抗原库的内在局限性。
