Functional role of HLA class I cell-surface molecules in human T-lymphocyte activation and proliferation.

Functional role of HLA class I cell-surface molecules in human T-lymphocyte activation and proliferation.
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HLA I 类细胞表面分子在人 T 淋巴细胞活化和增殖中的功能作用。

DOI:
10.1073/pnas.83.12.4446
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发表时间:
1986
影响因子:
11.1
通讯作者:
Kornbluth,J
Kornbluth,J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Taylor,DS;Nowell,PC;Kornbluth,J

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这项研究讨论了主要组织相容性复合体编码的I类分子在人类淋巴细胞激活和增殖中的作用。我们研究了针对人类白细胞抗原A和B位点基因产物的抗体对丝裂原刺激的外周血单个核细胞(PBMC)亚群的影响。三种单独衍生的、具有良好特性的抗人类白细胞抗原I类单抗可抑制OKT3或钙离子载体离子载体离子霉素刺激的人PBMC的增殖。针对人类白细胞抗原-A、-B和-C基因产物的抗体(W6/32)和针对人类白细胞抗原-B基因产物的抗体(4E)对任何一种有丝分裂原诱导的增殖抑制70-90%。HLAA位点特异性抗体(131)虽然抑制离子霉素诱导的增殖达80-90%,但在OKT3刺激下的效果要差得多。这种抑制作用主要影响T4+和T8+细胞,而不是由DR+辅助细胞介导。这些抗体的抑制作用与细胞培养上清液中IL-2活性降低、IL-2受体表达降低、转铁蛋白受体表达降低有关,但不能被外源性IL-2所抑制。我们的结果提示,人类白细胞抗原-I类分子直接参与了人类淋巴细胞活化和增殖的早期关键事件。
This investigation addressed the role of major histocompatibility complex-encoded class I molecules in the activation and proliferation of human lymphocytes. We studied the effect of antibodies specific for HLA-A and HLA-B locus gene products on mitogen-stimulated peripheral blood mononuclear cell (PBMC) subpopulations. Three individually derived, well-characterized anti-HLA class I monoclonal antibodies were demonstrated to inhibit the proliferation of human PBMC stimulated by either OKT3 or the calcium ionophore ionomycin. The antibody directed against HLA-A, -B, and -C locus gene products (W6/32) and the antibody directed against HLA-B locus gene products (4E) inhibited proliferation induced by either mitogen by 70-90%. The HLA-A locus-specific antibody (131), though inhibiting ionomycin-induced proliferation by 80-90%, was much less effective when OKT3 was the stimulus. The inhibition affected T4+ and T8+ cells and was not mediated by DR+ accessory cells. The inhibitory effect of these antibodies was associated with a decrease in the level of interleukin 2 activity present in culture supernatants, decreased interleukin 2 receptor expression, and decreased transferrin receptor expression and was not overcome by the addition of exogenous interleukin 2. Our results suggest that HLA class I molecules are directly involved in the early critical events of human lymphocyte activation and proliferation.