Ladiges W C, Pesando J M, Severns E, Longton G, Deeg H J, Storb R
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Transplantation. 1988 Feb;45(2):484-8. doi: 10.1097/00007890-198802000-00048.
Twenty-three of 37 anti-Ia McAb reactive with human B cells, as determined by indirect immunocytofluorescence, were shown to be reactive with canine peripheral blood mononuclear cells (PBMC). Using a panel of human B cell lines that differ in their expression of HLA-DR, -DP, and -DQ molecules, it was shown that 15 of these antibodies identify HLA-DR and DP molecules (i.e., broadly reactive), while 22 identify only HLA-DR molecules. Fourteen of the 15 broadly reactive McAb were reactive with canine PBMC while only 9 of the 22 HLA-DR-specific McAb reacted with canine PBMC, suggesting that broadly reactive anti-Ia McAb are much more likely to react with canine cells than narrowly reactive McAb. Ten of the canine reactive McAb that were shown to identify typical Ia bimolecular structures on canine cells using immune precipitation analysis were tested for blocking activity in the canine mixed lymphocyte culture (MLC). All four of the broadly reactive McAb (B1F6, J-70, 9-49, and HB10a) plus two of the six narrowly reactive McAbs (H81.98.21 and H40.164.3) blocked the canine MLC when added to culture wells on day 0, suggesting that inhibition may be related to the specificity of the anti-Ia McAb employed. Since the MLC may reflect cellular interactions occurring during graft-versus-host disease, this assay may be useful for screening functionally relevant broadly reactive McAb in experimental canine bone marrow transplantation studies. These data suggest that the dog may be a useful model to study anti-Ia immunotherapy.
通过间接免疫细胞荧光法测定,37种与人类B细胞反应的抗Ia单克隆抗体(McAb)中有23种被证明与犬外周血单个核细胞(PBMC)反应。使用一组在HLA - DR、- DP和 - DQ分子表达上存在差异的人类B细胞系,结果表明其中15种抗体识别HLA - DR和DP分子(即具有广泛反应性),而22种仅识别HLA - DR分子。15种具有广泛反应性的McAb中有14种与犬PBMC反应,而22种HLA - DR特异性McAb中只有9种与犬PBMC反应,这表明具有广泛反应性的抗Ia McAb比反应狭窄的McAb更有可能与犬细胞反应。使用免疫沉淀分析表明,在犬细胞上识别典型Ia双分子结构的10种与犬反应的McAb在犬混合淋巴细胞培养(MLC)中进行阻断活性测试。当在第0天加入培养孔时,所有4种具有广泛反应性的McAb(B1F6、J - 70、9 - 49和HB10a)以及6种反应狭窄的McAb中的2种(H81.98.21和H40.164.3)阻断了犬MLC,这表明抑制作用可能与所使用的抗Ia McAb的特异性有关。由于MLC可能反映移植物抗宿主病期间发生的细胞相互作用,该试验可能有助于在实验性犬骨髓移植研究中筛选功能相关的具有广泛反应性的McAb。这些数据表明,狗可能是研究抗Ia免疫疗法的有用模型。