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混合白细胞培养反应中反应细胞活性的抑制。I. B7抗体与HLA - B8交叉反应的证据。

Inhibition of responder cell activity in mixed leukocyte culture reactions. I. Evidence of cross-reactivity of B7-antibody with HLA-B8.

作者信息

de Rooij-Doyer E, Bruning J W, van Rood J J

出版信息

Tissue Antigens. 1981 Sep;18(3):154-65. doi: 10.1111/j.1399-0039.1981.tb01378.x.

Abstract

In a previous report we described a human allo-antiserum which showed MHC restricted dual specific inhibition of mixed leukocyte culture (MLC) reactions (de Rooij et al. 1980). Responder cells were preincubated with the antiserum and washed. Inhibition of MLC reactions occurred if HLA-B8 positive responder cells and HLA-B7 or B40 positive stimulator cells were used. The mechanism of inhibition by this antiserum was investigated and described in this report. The results strongly suggested that the observed inhibition was due to HLA-B7 specific antibody molecules cross-reacting with HLA-B8 antigens. We decided on the following mechanism: HLA-B7 specific antibody molecules bind to HLA-B8 antigens on responder cells at 4 degrees C. Bound antibody molecules area readily released at 37 degrees C and the bind preferentially to HLA-B7 or -B40 positive stimulator cells. Stimulator cells are then lysed by antibody dependent cellular cytotoxicity (ADCC), resulting in impaired MLC reaction. This conclusion was derived from the following observations: 1. HLA-B7 positive cells could be lysed due to antibody molecules bound to B8 positive cells: a. Cells coated with antibody molecules lysed B7 or B40 positive target cells. b. Antibody molecules released from B8 positive cells lysed B7 or B40 positive target cells in ADCC. 2. The active antibody molecules were HLA-B7 specific: a. The inhibiting antibody molecules in the antiserum could be absorbed on and eluted from HLA-B7 positive platelets (de Rooij et al. 1980). b. Antibody molecules bound to and released from HLA-B8 positive cells carried the same B7 specific inhibiting and cytotoxic activity as the original antiserum. 3. The site of recognition on HLA-B8 positive cells is the HLA-B8 antigen: a. F(ab')2 preparations from HLA-B8 and -Bw6 specific antisera inhibited antibody binding to B8 positive cells. b. Antibody binding was not restricted to B, T, FcR+, FcR- or non adherent cell subpopulations. 4. The antibody molecules bind to B8 positive cells with the antigen binding site and not with the Fc part of the molecule: a. Antibody binding could be blocked partially with a F(ab')2 preparation from the original antiserum but not with a Fc preparation. b. The antigen binding site of antibody molecules bound to HLA-B8 positive cells was not freely available, since the MLC inhibiting activity of sensitised B8 positive cells could not be blocked by soluble HLA-B7 antigens. c. The antiserum was cytotoxic for HLA-B8 positive target cells in ADCC. The observed inhibition of MLC by antibody molecules with apparent dual specificity is thus the consequence of a shared or a similar antigenic determinant of HLA-B7 and HLA-B8 antigen molecules.

摘要

在之前的一份报告中,我们描述了一种人同种异体抗血清,它对混合淋巴细胞培养(MLC)反应表现出MHC限制的双重特异性抑制作用(de Rooij等人,1980年)。将应答细胞与抗血清预孵育并洗涤。如果使用HLA - B8阳性应答细胞和HLA - B7或B40阳性刺激细胞,则会发生MLC反应的抑制。本报告研究并描述了这种抗血清的抑制机制。结果强烈表明,观察到的抑制是由于HLA - B7特异性抗体分子与HLA - B8抗原发生交叉反应所致。我们确定了以下机制:HLA - B7特异性抗体分子在4℃时与应答细胞上的HLA - B8抗原结合。结合的抗体分子在37℃时很容易释放,并优先与HLA - B7或 - B40阳性刺激细胞结合。然后刺激细胞被抗体依赖性细胞毒性(ADCC)裂解,导致MLC反应受损。这一结论源于以下观察结果:1. 由于与B8阳性细胞结合的抗体分子,HLA - B7阳性细胞可被裂解:a. 被抗体分子包被的细胞裂解B7或B40阳性靶细胞。b. 从B8阳性细胞释放的抗体分子在ADCC中裂解B7或B40阳性靶细胞。2. 活性抗体分子是HLA - B7特异性的:a. 抗血清中的抑制性抗体分子可被HLA - B7阳性血小板吸附并洗脱(de Rooij等人,1980年)。b. 与HLA - B8阳性细胞结合并释放的抗体分子具有与原始抗血清相同的B7特异性抑制和细胞毒性活性。3. HLA - B8阳性细胞上的识别位点是HLA - B8抗原:a. 来自HLA - B8和 - Bw6特异性抗血清的F(ab')2制剂抑制抗体与B8阳性细胞的结合。b. 抗体结合不限于B、T、FcR +、FcR - 或非黏附细胞亚群。4. 抗体分子以抗原结合位点而非分子的Fc部分与B8阳性细胞结合:a. 抗体结合可被原始抗血清的F(ab')2制剂部分阻断,但不能被Fc制剂阻断。b. 与HLA - B8阳性细胞结合的抗体分子的抗原结合位点并非自由可用,因为致敏B8阳性细胞的MLC抑制活性不能被可溶性HLA - B7抗原阻断。c. 该抗血清在ADCC中对HLA - B8阳性靶细胞具有细胞毒性。因此,观察到的具有明显双重特异性的抗体分子对MLC的抑制是HLA - B7和HLA - B8抗原分子共享或相似抗原决定簇的结果。

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