Park S H, Roark J H, Bendelac A
Department of Molecular Biology, Princeton University, NJ 08544, USA.
J Immunol. 1998 Apr 1;160(7):3128-34.
Although there is evidence that some members of the CD1 gene family may present particular types of foreign Ags, such as mycobacterial lipid Ags or synthetic hydrophobic peptides, to alphabeta T cells, most CD1 isotypes share the unusual property of being recognized by a high frequency of naturally autoreactive alphabeta T cells. In the case of mouse CD1.1 and its human counterpart CD1d, a significant fraction of the autoreactive T cells express semi-invariant TCRs. CD1.1-specific T cells have a restricted tissue distribution and very promptly secrete a large panel of potent cytokines, including IL-4 and IFN-gamma, upon primary activation through their TCR, suggesting that they might regulate some immune responses in these tissues. We show here that their autorecognition of mouse CD1.1 is highly dependent upon the cell type in which CD1.1 is expressed. For example, some of these T cells only respond to CD1.1 expressed by splenic dendritic cells, some respond preferentially to cortical thymocytes, and others respond to splenic B cells. Tissue specificity of CD1.1 recognition is also observed with various cell lines transfected with CD1.1 cDNA. These results show that different CD1.1 self Ags are expressed in different tissues and can be specifically recognized by autoreactive T cells. They suggest that CD1.1 may be naturally associated with a variety of self ligands that overlap only partially in different cell types.
尽管有证据表明,CD1基因家族的某些成员可能会将特定类型的外源抗原,如分枝杆菌脂类抗原或合成疏水肽,呈递给αβ T细胞,但大多数CD1同种型具有一种不同寻常的特性,即能被高频率的天然自身反应性αβ T细胞识别。就小鼠CD1.1及其人类对应物CD1d而言,相当一部分自身反应性T细胞表达半不变TCR。CD1.1特异性T细胞具有受限的组织分布,并且在通过其TCR进行初次激活后,会非常迅速地分泌大量强效细胞因子,包括IL-4和IFN-γ,这表明它们可能在这些组织中调节某些免疫反应。我们在此表明,它们对小鼠CD1.1的自身识别高度依赖于表达CD1.1的细胞类型。例如,其中一些T细胞仅对脾树突状细胞表达的CD1.1有反应,一些则优先对皮质胸腺细胞有反应,还有一些对脾B细胞有反应。在用CD1.1 cDNA转染的各种细胞系中也观察到了CD1.1识别的组织特异性。这些结果表明,不同的CD1.1自身抗原在不同组织中表达,并且能被自身反应性T细胞特异性识别。它们提示,CD1.1可能天然地与多种自身配体相关联,这些自身配体在不同细胞类型中仅部分重叠。