Sciammas R, Bluestone J A
Committee on Immunology, Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA.
J Immunol. 1998 Nov 15;161(10):5187-92.
Despite the description of numerous antigenic ligands recognized by TCRgammadelta cells, detailed information concerning the structural nature of these antigenic epitopes is lacking. In addition, the recent descriptions of human TCRgammadelta cells recognizing mycobacterium-derived low m.w. lipid molecules confirms that the spectrum and nature of biologic structures that are capable of being recognized by TCRgammadelta cells are unclear. We have previously described a murine TCRgammadelta cell clone, TgI4.4, that is reactive to herpes simplex virus (HSV)-1 glycoprotein I (gI). Unlike TCRalphabeta-mediated, MHC-restricted Ag recognition but similar to Ig Ag recognition, TgI4.4 recognizes purified gI directly, in the absence of Ag processing or presentation. Since gI is a complex glycoprotein, the nature of the antigenic epitope was investigated. First, gI recognition by TgI4.4 is conformationally dependent, as revealed by denaturation and proteolytic experiments. Secondly, the epitope recognized by TgI4.4 was mapped to the amino terminus by using insertion mutants of gI. Lastly, TgI4.4 recognizes the gI protein directly since completely deglycosylated forms of gI are efficiently recognized. Therefore, TCRgammadelta cells are capable of recognizing a variety of molecular structures, including proteins. The ability of TgI4.4 to recognize a nonglycosylated form of gI suggests that HSV-1 recognition by TCRgammadelta cells in vivo is not limited by cell-specific glycosylation patterns or glycosylation-dependent conformational influences.
尽管已描述了众多可被TCRγδ细胞识别的抗原配体，但关于这些抗原表位的结构性质的详细信息仍很缺乏。此外，最近关于人类TCRγδ细胞识别分枝杆菌来源的低分子量脂质分子的描述证实，能够被TCRγδ细胞识别的生物结构的范围和性质尚不清楚。我们之前描述过一个小鼠TCRγδ细胞克隆TgI4.4，它对单纯疱疹病毒1型（HSV-1）糖蛋白I（gI）具有反应性。与TCRαβ介导的、MHC限制的抗原识别不同，但与Ig抗原识别相似，TgI4.4在没有抗原加工或呈递的情况下直接识别纯化的gI。由于gI是一种复杂的糖蛋白，因此对其抗原表位的性质进行了研究。首先，变性和蛋白水解实验表明，TgI4.4对gI的识别依赖于构象。其次，通过使用gI的插入突变体将TgI4.4识别的表位定位到氨基末端。最后，TgI4.4直接识别gI蛋白，因为完全去糖基化形式的gI能被有效识别。因此，TCRγδ细胞能够识别包括蛋白质在内的多种分子结构。TgI4.4识别非糖基化形式gI的能力表明，体内TCRγδ细胞对HSV-1的识别不受细胞特异性糖基化模式或糖基化依赖性构象影响的限制。
