Pacasova R, Martinozzi S, Boulouis H J, Ulbrecht M, Vieville J C, Sigaux F, Weiss E H, Pla M
Mouse Immunogenetics, U462, Institut National de la Santé et de la Recherche Médicale, Saint-Louis Hospital, Paris, France.
J Immunol. 1999 May 1;162(9):5190-6.
We have introduced the gene (E*01033) encoding the heavy chain of the human nonclassical MHC class I Ag, HLA-E, into the mouse genome. Two founder mice carry a 21-kb fragment, the others bear an 8-kb fragment. Each of the founder mice was mated to mice of an already established C57BL/10 transgenic line expressing human beta2-microglobulin (beta2m). Cell surface HLA-E was detected on lymph node cells by flow cytometry only in the presence of endogenous human beta2m. However, HLA-E-reactive mouse CTL (H-2-unrestricted) lysed efficiently the target cells originating from HLA-E transgenic mice without human beta2m, showing that the HLA-E protein can be transported to the cell surface in the absence of human beta2m, presumably by association with murine beta2m. Rejection of skin grafts from HLA-E transgenic mice demonstrates that HLA-E behaves as a transplantation Ag in mice. HLA-E transgenic spleen cells are effective in stimulating an allogeneic CTL response in normal and human classical class I (HLA-B27) transgenic mice. Furthermore, results from split-well analysis indicate that the majority of the primary in vivo-induced CTL recognizes HLA-E as an intact molecule (H-2-unrestricted recognition) and not as an HLA-E-derived peptide presented by a mouse MHC molecule, although a small fraction (ranging from 4 to 21%) of the primary in vivo-induced CTL is able to recognize HLA-E in an H-2-restricted manner. Based on these observations, we conclude that HLA-E exhibits alloantigenic properties that are indistinguishable from classical HLA class I molecules when expressed in transgenic mice.
我们已将编码人类非经典MHC I类抗原HLA - E重链的基因（E*01033）导入小鼠基因组。两只奠基小鼠携带一个21 kb的片段，其他小鼠携带一个8 kb的片段。每只奠基小鼠都与已建立的表达人β2 - 微球蛋白（β2m）的C57BL/10转基因品系的小鼠交配。仅在内源性人β2m存在的情况下，通过流式细胞术在淋巴结细胞上检测到细胞表面的HLA - E。然而，HLA - E反应性小鼠CTL（H - 2非限制性）能有效裂解源自无人β2m的HLA - E转基因小鼠的靶细胞，表明HLA - E蛋白在无人β2m的情况下可能通过与小鼠β2m结合而被转运到细胞表面。对来自HLA - E转基因小鼠的皮肤移植的排斥表明HLA - E在小鼠中表现为移植抗原。HLA - E转基因脾细胞能有效刺激正常和人经典I类（HLA - B27）转基因小鼠的同种异体CTL反应。此外，分孔分析结果表明，大多数体内初次诱导的CTL将HLA - E识别为完整分子（H - 2非限制性识别），而不是由小鼠MHC分子呈递的HLA - E衍生肽，尽管一小部分（4%至21%）体内初次诱导的CTL能够以H - 2限制性方式识别HLA - E。基于这些观察结果，我们得出结论，当在转基因小鼠中表达时，HLA - E表现出与经典HLA I类分子无法区分的同种抗原特性。
