Expression of the human MHC, HLA-DQW6 genes alters the immune response in C57BL/6 mice.
Expression of the human MHC, HLA-DQW6 genes alters the immune response in C57BL/6 mice.
复制标题
人类 MHC、HLA-DQW6 基因的表达改变了 C57BL/6 小鼠的免疫反应。
作者：
Y. Nishimura;T. Iwanaga;T. Inamitsu;Y. Yanagawa;M. Yasunami;A. Kimura;K. Hirokawa;T. Sasazuki
为了获得HLA II类分子在调节免疫反应中关键作用的直接证据，将来自HLA-Dw12单倍型的HLA-DQw6的α链和β链基因组基因引入C57BL/6（B6）品系小鼠中，获得了HLA-DQw6转基因小鼠品系。转基因表达的组织特异性与鼠 I-Ab 基因的组织特异性非常相似。 DQw6 分子在脾细胞中的 B 细胞和巨噬细胞上表达，约 30% 至 40% 的 I-Ab+ 脾细胞呈 DQw6 阳性。 HLA-DQw6 转基因 B6 小鼠变得对 DQw6 分子具有耐受性，如 DQw6 分子特异性的 MLR 和抗体产生所证明。 HLA-DQw6转基因B6小鼠对链球菌细胞壁抗原（SCW）表现出强烈的免疫反应，而B6小鼠对SCW的反应较低。 SCW 特异性 T 细胞系是从转基因小鼠中建立的，该 T 细胞系在小鼠 L 细胞转染子或人单核细胞上表达的 HLA-DQw6 分子的背景下识别 SCW。抗HLA-DQ mAb 抑制了来自转基因小鼠的致敏淋巴结 T 细胞和 SCW 特异性 T 细胞系对 SCW 的增殖反应。因此，很明显HLA-DQw6基因在这些转基因小鼠中充当主要组织相容性基因。
In an attempt to obtain direct evidence for the critical role of HLA class II molecules in regulating the immune response, genomic genes for alpha- and beta-chains of HLA-DQw6 from HLA-Dw12 haplotype were introduced into the C57BL/6 (B6) strain of mouse and a line of HLA-DQw6 transgenic mouse was obtained. Tissue specificity of the expression of the transgenes was much the same as that of murine I-Ab genes. DQw6 molecules were expressed on B cells and macrophages in spleen cells and about 30 to 40% of the I-Ab+ spleen cells were positive for DQw6. The HLA-DQw6 transgenic B6 mouse became tolerant to the DQw6 molecules, as evidenced by the MLR and antibody production specific to the DQw6 molecules. The HLA-DQw6 transgenic B6 mouse showed a strong immune response to streptococcal cell wall antigen (SCW), whereas the B6 mouse was a low responder to SCW. The SCW-specific T cell line was established from the transgenic mouse and this T cell line recognized SCW in the context of HLA-DQw6 molecules expressed on the mouse L cell transfectant or on human monocytes. The proliferative response to SCW of primed lymph node T cells and the SCW-specific T cell line derived from the transgenic mice was inhibited by anti-HLA-DQ mAb. Thus, it is clear that the HLA-DQw6 genes acted as major histocompatibility genes in these transgenic mice.