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针对Lyt-2的单克隆抗体对T细胞介导的细胞溶解作用的抑制:克隆水平上抑制作用的异质性

Inhibition of T cell-mediated cytolysis by monoclonal antibodies directed against Lyt-2: heterogeneity of inhibition at the clonal level.

作者信息

MacDonald H R, Thiernesse N, Cerottini J C

出版信息

J Immunol. 1981 May;126(5):1671-5.

PMID:6452474
Abstract

The inhibitory effect of monoclonal anti-Lyt-2 antibodies on T cell-mediated cytolysis has been investigated at the clonal level. In agreement with previous reports from several laboratories, populations of cytolytic T lymphocytes (CTL) generated in vitro in mixed leukocyte cultures (MLC) were reversibly inhibited by monoclonal anti-Lyt-2 antibodies in a dose-dependent fashion. However, when alloimmune peritoneal exudate lymphocytes (PEL) were used as a source of CTL, little or no inhibitory effect of anti-Lyt-2 antibodies on cytolysis was observed. A series of CTL clones derived from MLC or PEL populations was also tested for inhibition of cytolysis by anti-Lyt-2 antibodies. In agreement with results obtained at the population level, most MLC-derived clones (81%) were strongly inhibited by the reagent, whereas few PEL clones (15%) were inhibited. Several of these clones were expanded and maintained in culture without loss of their "inhibition phenotype." Flow cytofluorometric analysis using the same monoclonal anti-Lyt-2 antibodies further revealed that both inhibited and uninhibited clones expressed comparable amounts of Lyt-2 antigen. These results provide direct evidence that inhibition of CTL by anti-Lyt-2 antibodies is heterogeneous at the clonal level. The possibility that this heterogeneity may be related to avidity of antigen receptors is discussed.

摘要

已在克隆水平上研究了单克隆抗Lyt-2抗体对T细胞介导的细胞溶解作用的抑制效果。与几个实验室先前的报道一致,在混合淋巴细胞培养(MLC)中体外产生的细胞毒性T淋巴细胞(CTL)群体,被单克隆抗Lyt-2抗体以剂量依赖方式可逆性抑制。然而,当同种免疫腹膜渗出淋巴细胞(PEL)用作CTL来源时,未观察到抗Lyt-2抗体对细胞溶解有明显抑制作用。还测试了一系列源自MLC或PEL群体的CTL克隆对细胞溶解的抑制情况。与群体水平获得的结果一致,大多数源自MLC的克隆(81%)被该试剂强烈抑制,而很少有PEL克隆(15%)被抑制。其中几个克隆在培养中得以扩增并维持,且未丧失其“抑制表型”。使用相同的单克隆抗Lyt-2抗体进行的流式细胞荧光分析进一步显示,被抑制和未被抑制的克隆表达的Lyt-2抗原量相当。这些结果提供了直接证据,表明抗Lyt-2抗体对CTL的抑制在克隆水平上是异质性的。本文讨论了这种异质性可能与抗原受体亲和力相关的可能性。

相似文献

1
Inhibition of T cell-mediated cytolysis by monoclonal antibodies directed against Lyt-2: heterogeneity of inhibition at the clonal level.针对Lyt-2的单克隆抗体对T细胞介导的细胞溶解作用的抑制:克隆水平上抑制作用的异质性
J Immunol. 1981 May;126(5):1671-5.
2
Studies on the cytolytic attack mechanism of the cytotoxic T lymphocyte (CTL): preparation of antisera against cellfree cytosolic extracts of a CTL clone capable of blocking the lethal hit stage of CTL cytolysis and analysis of the cytolytic structure.细胞毒性T淋巴细胞(CTL)的溶细胞攻击机制研究:制备针对能够阻断CTL细胞溶解致死阶段的CTL克隆的无细胞胞质提取物的抗血清,并分析溶细胞结构。
J Immunol. 1985 Jul;135(1):53-62.
3
Clonal analysis of cytolytic T lymphocyte-mediated lysis of target cells with inducible antigen expression: correlation between antigen density and requirement for Lyt-2/3 function.对具有诱导性抗原表达的靶细胞进行细胞溶解T淋巴细胞介导的裂解的克隆分析:抗原密度与Lyt-2/3功能需求之间的相关性。
J Immunol. 1985 Aug;135(2):892-9.
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A rat anti-mouse T4 monoclonal antibody (H129.19) inhibits the proliferation of Ia-reactive T cell clones and delineates two phenotypically distinct (T4+, Lyt-2,3-, and T4-, Lyt-2,3+) subsets among anti-Ia cytolytic T cell clones.一种大鼠抗小鼠T4单克隆抗体(H129.19)可抑制Ia反应性T细胞克隆的增殖,并在抗Ia细胞毒性T细胞克隆中区分出两个表型不同的亚群(T4+、Lyt-2,3-和T4-、Lyt-2,3+)。
J Immunol. 1984 Jun;132(6):2775-82.
5
Effects of monoclonal antibodies directed against murine T lymphocyte cell surface antigens on lymphokine production by cloned T lymphocytes reactive with class I MHC or Mls alloantigens.针对小鼠T淋巴细胞细胞表面抗原的单克隆抗体对与I类主要组织相容性复合体(MHC)或Mls同种异体抗原反应的克隆T淋巴细胞产生淋巴因子的影响。
J Immunol. 1984 Oct;133(4):2051-7.
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Inhibition of cytolytic T lymphocyte clones reactive with Moloney leukemia virus-associated antigens by monoclonal antibodies: a direct approach to the study of H-2 restriction.单克隆抗体对与莫洛尼白血病病毒相关抗原起反应的细胞溶解T淋巴细胞克隆的抑制作用:H-2限制性研究的直接方法
J Immunol. 1981 Feb;126(2):482-5.
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Effects of anti-Lyt-2 and anti-L3T4 monoclonal antibodies on the function of cytotoxic T lymphocyte/helper T lymphocyte hybrid T cell clones.抗Lyt-2和抗L3T4单克隆抗体对细胞毒性T淋巴细胞/辅助性T淋巴细胞杂交T细胞克隆功能的影响。
J Immunol. 1988 Sep 15;141(6):1808-12.
8
Monoclonal anti-Lyt-2 antibodies block the activation of cytolytic T lymphocyte precursors.单克隆抗Lyt-2抗体可阻断细胞毒性T淋巴细胞前体的激活。
J Immunol. 1983 Apr;130(4):1552-5.
9
Human cytotoxic T cell structures associated with expression of cytolysis. I. Analysis at the clonal cell level of the cytolysis-inhibiting effect of 7 monoclonal antibodies.与细胞溶解表达相关的人细胞毒性T细胞结构。I. 7种单克隆抗体细胞溶解抑制作用的克隆细胞水平分析。
Eur J Immunol. 1982 Sep;12(9):739-47. doi: 10.1002/eji.1830120908.
10
Cytolytic T lymphocyte clones that proliferate autonomously to specific alloantigenic stimulation. II. Relationship of the Lyt-2 molecular complex to cytolytic activity, proliferation, and lymphokine secretion.对特定同种异体抗原刺激能自主增殖的细胞溶解性T淋巴细胞克隆。II. Lyt-2分子复合物与细胞溶解活性、增殖及淋巴因子分泌的关系。
J Immunol. 1983 Apr;130(4):1545-51.

引用本文的文献

1
Allogeneic tumor rejection induced by the intravenous injection of Lyt-2+ cytolytic T lymphocyte clones.静脉注射Lyt-2+溶细胞性T淋巴细胞克隆诱导的同种异体肿瘤排斥反应。
J Exp Med. 1982 Oct 1;156(4):1280-5. doi: 10.1084/jem.156.4.1280.
2
Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of cytotoxic T lymphocytes specific for SB antigens.OKT4分子可能参与T细胞对II类HLA抗原的识别。来自针对SB抗原的细胞毒性T淋巴细胞研究的证据。
J Exp Med. 1982 Oct 1;156(4):1065-76. doi: 10.1084/jem.156.4.1065.
3
Clonal heterogeneity in the functional requirement for Lyt-2/3 molecules on cytolytic T lymphocytes: analysis by antibody blocking and selective trypsinization.
细胞毒性T淋巴细胞上Lyt-2/3分子功能需求的克隆异质性:通过抗体阻断和选择性胰蛋白酶消化进行分析。
J Exp Med. 1982 Dec 1;156(6):1711-22. doi: 10.1084/jem.156.6.1711.
4
Significance of Lyt phenotypes: Lyt2 antibodies block activities of T cells that recognize class 1 major histocompatibility complex antigens regardless of their function.Lyt表型的意义:Lyt2抗体可阻断识别1类主要组织相容性复合体抗原的T细胞的活性,无论其功能如何。
Proc Natl Acad Sci U S A. 1981 Nov;78(11):7101-5. doi: 10.1073/pnas.78.11.7101.
5
Clonal heterogeneity in the requirement for T3, T4, and T8 molecules in human cytolytic T lymphocyte function.人细胞毒性T淋巴细胞功能中对T3、T4和T8分子需求的克隆异质性。
J Exp Med. 1984 Mar 1;159(3):921-34. doi: 10.1084/jem.159.3.921.
6
Possible involvement of the T4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of CTL-target cell binding.T4分子可能参与T细胞对II类HLA抗原的识别。来自细胞毒性T淋巴细胞-靶细胞结合研究的证据。
J Exp Med. 1984 Mar 1;159(3):783-97. doi: 10.1084/jem.159.3.783.
7
Direct transfer of antigen-specific cytolytic activity to noncytolytic cells upon fusion with liposomes derived from cytolytic T cell clones.与源自细胞溶解性T细胞克隆的脂质体融合后,抗原特异性细胞溶解活性直接转移至非细胞溶解性细胞。
J Exp Med. 1984 Jan 1;159(1):261-75. doi: 10.1084/jem.159.1.261.
8
Mouse Lyt-2 antigen: evidence for two heterodimers with a common subunit.小鼠Lyt-2抗原:存在两种含共同亚基的异二聚体的证据。
Proc Natl Acad Sci U S A. 1982 Apr;79(8):2654-7. doi: 10.1073/pnas.79.8.2654.
9
Expression and function of CD8 in a murine T cell hybridoma.CD8在小鼠T细胞杂交瘤中的表达与功能
J Exp Med. 1987 Dec 1;166(6):1747-57. doi: 10.1084/jem.166.6.1747.
10
Modulation in vivo of Lyt 2 antigen expression on T cells by anti-Lyt 2 antibody: effects on Con A-induced unresponsiveness.抗Lyt 2抗体对T细胞上Lyt 2抗原表达的体内调节:对刀豆蛋白A诱导的无反应性的影响。
Immunology. 1986 Oct;59(2):181-6.