Recognition of major histocompatibility complex class II antigens by two anti-HLA-DR monoclonal antibodies on canine marrow cells correlates with effects on in vitro and in vivo hematopoiesis.
Recognition of major histocompatibility complex class II antigens by two anti-HLA-DR monoclonal antibodies on canine marrow cells correlates with effects on in vitro and in vivo hematopoiesis.
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犬骨髓细胞上的两种抗 HLA-DR 单克隆抗体对主要组织相容性复合物 II 类抗原的识别与对体外和体内造血作用的影响相关。
DOI：
10.1097/00007890-199910270-00017
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发表时间：
1999
期刊：
影响因子：
6.2
通讯作者：
Deeg,HJ
中科院分区：
文献类型：
--
作者：
Yamaguchi,M;McSweeney,PA;Kimball,L;Gersuk,G;Hong,DS;Kwok,W;Storb,R;Beckham,C;Deeg,HJ
背景：主要组织相容性复合物 II 类抗原在造血过程中的作用尚未明确。我们已经证明，体外从犬骨髓中去除 HLA-DR+ 细胞（例如，通过抗 HLA-DR 单克隆抗体 [mAb] H81.9 和补体）会阻止造血恢复。体内施用相同的 mAb H81。 9 未经操作的自体骨髓移植后导致移植失败。体外单克隆抗体 H81。 9 抑制短期和长期骨髓培养物的集落形成。方法和结果我们研究了另一种 mAb Ca1.9 的作用。 41，它还识别人类 (HLA-DR) 和犬主要组织相容性复合体 II 类抗原的非多态性决定簇，但与 mAb H81 相比，与犬外周血和骨髓中的细胞谱更窄。 9（和其他抗 HLA-DR 单克隆抗体）。与所有其他测试的抗 HLA-DR mAb 相比，Ca1. 41 不会干扰短期或长期骨髓培养中的集落形成，并且保留了一群具有低前向光散射的小单核细胞，这些细胞通过暴露于 mAb H81 细胞凋亡而被消除。 9. 这些靶细胞包括淋巴细胞和 CD34+ 造血前体细胞，通过 mAb H81 测定它们表达 MHC II 类分子。 9 但不是单克隆抗体 Ca1。 41. 此外，mAb H81 还发生跨膜信号传导和白细胞介素 1β mRNA 上调。 9 但不包括 Ca1。 41.用mAb Ca1体外溶细胞处理的自体骨髓移植。 41允许完全造血重建。此外，Ca1的体内施用。 41 移植后不会导致自体移植失败，正如使用 mAb H81 观察到的那样。 9.结论。这些结果支持这样的观点，即主要组织相容性复合物 II 类在早期造血前体细胞上表达，但识别取决于所使用的 mAb。初步研究表明 mAb H81.尽管 mAb Ca1.9 触发跨膜信号传导，导致白细胞介素 1β 上调和细胞凋亡。 41 没有。事实上，Ca1。 41 结合在外源不变链衍生肽存在的情况下被修饰，表明结合和信号传导都是肽依赖性的。
Background.The role of major histocompatibility complex class II antigens in hematopoiesis is not well defined. We have shown that in vitro depletion of HLA-DR+ cells from canine marrow (eg, by anti-HLA-DR monoclonal antibody [mAb] H81. 9 and complement) prevents hematopoietic recovery. In vivo administration of the same mAb H81. 9 after transplantation of unmanipulated autologous marrow results in graft failure. In vitro mAb H81. 9 inhibited colony formation from short-term and long-term marrow cultures.Methods and resultsWe investigated the effect of another mAb, Ca1. 41, which also recognizes nonpolymorphic determinants on human (HLA-DR) and canine major histocompatibility complex class II anti-gens but is reactive with a narrower spectrum of cells in both canine peripheral blood and marrow than mAb H81. 9 (and other anti-HLA-DR mAbs). In contrast to all other anti-HLA-DR mAbs tested, Ca1. 41 did not interfere with colony formation in short-term or long-term marrow cultures and spared a population of small mononuclear cells with low forward light scatter that was eliminated via apoptosis by exposure to mAb H81. 9. These target cells included lymphocytes and CD34+ hemopoietic precursors that expressed MHC class II molecules as determined by mAb H81. 9 but not by mAb Ca1. 41. In addition, transmembrane signaling and up-regulation of interleukin-1β mRNA occurred with mAb H81. 9 but not with Ca1. 41. Transplantation of autologous marrow treated in vitro cytolytically with mAb Ca1. 41 allowed for complete hematopoietic reconstitution. Further, in vivo administration of Ca1. 41 posttransplant did not lead to autologous graft failure as had been observed with mAb H81. 9.Conclusions.These results support the notion that major histocompatibility complex class II is expressed on early hematopoietic precursor cells but recognition is dependent upon the mAb used. Preliminary studies show that mAb H81. 9 triggered transmembrane signaling, resulting in up-regulation of interleukin-1β and apoptosis, although mAb Ca1. 41 did not. The fact that Ca1. 41 binding was modified in the presence of exogenous invariant chain-derived peptide suggests that both binding and signaling are peptide dependent.