The human lymphocyte function-associated (HLFA) antigen and a related macrophage differentiation antigen (HMac-1): functional effects of subunit-specific monoclonal antibodies.

The human lymphocyte function-associated (HLFA) antigen and a related macrophage differentiation antigen (HMac-1): functional effects of subunit-specific monoclonal antibodies.
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DOI:
10.4049/jimmunol.134.5.3272
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发表时间:
1985-05
影响因子:
4.4
通讯作者:
J. Hildreth;J. August
J. Hildreth;J. August
中科院分区:
医学2区
文献类型:
--
作者:
J. Hildreth;J. August

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使用5种与这些蛋白质反应的单克隆抗体,分析了人淋巴细胞功能相关抗原(HLFA)和人Mac-1抗原(HMac-1)的α-和β-亚基之间的结构和功能关系。这些抗体的特异性进行了检查,从125 I标记的细胞和纯化的HLFA和HMac-1抗原的蛋白质的免疫沉淀。三种抗体与蛋白质的Mr 95,000共同β亚基反应,并且还共沉淀Mr 175,000 HLFA α亚基、Mr 165,000 HMac-1 α亚基和Mr 150,000的第三多肽α亚基。其他抗体对HLFA或HMac-1的α-亚基上存在的非交叉反应性表位具有特异性。这些特异性在连续免疫沉淀研究中得到证实。肽图谱显示HLFA和HMac-1的β亚基是相同的,而两个α亚基差异很大。HLFA α亚单位特异性单克隆抗体抑制植物血凝素刺激、混合淋巴细胞反应、细胞溶解性T淋巴细胞介导的杀伤和破伤风类毒素刺激,但不影响自然杀伤细胞介导的杀伤或补体受体3型功能。HMac-1 α亚单位特异性单克隆抗体抑制补体受体3型功能,但对T细胞或自然杀伤细胞功能没有影响。针对β亚基的三种单克隆抗体抑制所有测试功能,包括T细胞、自然杀伤细胞和补体受体3型活性。结果表明HLFA和HMac-1分子的功能可能由α亚基决定,并且共同的β亚基也具有功能重要的表位。
The structural and functional relations between the alpha- and beta-subunits of the human lymphocyte function-associated antigen (HLFA) and the human Mac-1 antigen (HMac-1) have been analyzed with the use of five monoclonal antibodies that react with these proteins. The specificities of these antibodies were examined by immunoprecipitation of proteins from 125I-labeled cells and purified HLFA and HMac-1 antigens. Three antibodies reacted with the Mr 95,000 common beta-subunit of the proteins, and also co-precipitated the Mr 175,000 HLFA alpha-subunit, the Mr 165,000 HMac-1 alpha-subunit, and a third polypeptide alpha-subunit of Mr 150,000. The other antibodies were specific to noncross-reactive epitopes present on the alpha-subunits of HLFA or HMac-1. These specificities were confirmed in sequential immunoprecipitation studies. Peptide mapping showed that the beta-subunits of HLFA and HMac-1 were identical, whereas the two alpha-subunits differed considerably. The HLFA alpha-subunit-specific monoclonal antibody inhibited phytohemagglutinin stimulation, the mixed lymphocytes reaction, cytolytic T lymphocyte-mediated killing, and tetanus toxoid stimulation, but did not affect natural killer cell-mediated killing or complement receptor type 3 function. The HMac-1 alpha-subunit-specific monoclonal antibody inhibited complement receptor type 3 function but had no effect on T cell or natural killer cell functions. Three monoclonal antibodies to the beta-subunit inhibited all functions tested, including T cell, natural killer cell, and complement receptor type 3 activities. The results suggest that the functions of the HLFA and HMac-1 molecules may be determined by the alpha-subunit, and that the common beta-subunit also bears functionally important epitopes.