Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells.

Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells.
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DOI:
10.1083/jcb.105.2.983
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发表时间:
1987-08
影响因子:
7.8
通讯作者:
Butcher, E C
Butcher, E C
中科院分区:
生物学1区
文献类型:
--
作者:
Jalkanen, S;Bargatze, R F;de los Toyos, J;Butcher, E C

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淋巴细胞的组织特异性归巢由专门的高内皮微静脉(HEV)指导。至少存在三种功能独立的淋巴细胞/HEV识别系统,控制循环淋巴细胞外渗到外周淋巴结、粘膜淋巴组织(派尔集合淋巴结或阑尾)和发炎关节的滑膜中。我们在此报道,能够抑制人淋巴细胞与一种或多种HEV类型结合的抗体识别由非阻断性单克隆抗体爱马仕-1定义的常见85- 95-kD淋巴细胞表面糖蛋白抗原。我们证明,MEL-14,一种针对小鼠淋巴结“归巢受体”的单克隆抗体,在功能上抑制人淋巴细胞与淋巴结HEV的结合,但不抑制粘膜或滑膜HEV的结合,并与85-95- kD爱马仕-1抗原交叉反应。此外,我们表明,爱马仕-3,一种新的抗体免疫产生的爱马仕-1抗原分离的粘膜HEV特异性细胞系,选择性地阻断淋巴细胞结合粘膜HEV。这种抑制的组织特异性表明MEL- 14和爱马仕-3分别阻断淋巴结和粘膜HEV的特异性淋巴细胞识别元件的功能。滑膜HEV的识别还涉及85-95-kD爱马仕-1抗原,因为针对分离的抗原产生的多克隆抗血清阻断所有三类淋巴细胞-HEV相互作用。从这些研究中,很可能爱马仕-1定义的85-95-kD糖蛋白类别包含一个相关但功能独立的HEV受体家族,或在物理和功能上与这些受体相关。这些发现意味着相关的分子机制参与了几个功能独立的细胞-细胞识别事件,直接淋巴细胞交通。
The tissue-specific homing of lymphocytes is directed by specialized high endothelial venules (HEV). At least three functionally independent lymphocyte/HEV recognition systems exist, controlling the extravasation of circulating lymphocytes into peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches or appendix), and the synovium of inflamed joints. We report here that antibodies capable of inhibiting human lymphocyte binding to one or more HEV types recognize a common 85- 95-kD lymphocyte surface glycoprotein antigen, defined by the non- blocking monoclonal antibody, Hermes-1. We demonstrate that MEL-14, a monoclonal antibody against putative lymph node "homing receptors" in the mouse, functionally inhibits human lymphocyte binding to lymph node HEV but not to mucosal or synovial HEV, and cross-reacts with the 85-95- kD Hermes-1 antigen. Furthermore, we show that Hermes-3, a novel antibody produced by immunization with Hermes-1 antigen isolated from a mucosal HEV-specific cell line, selectively blocks lymphocyte binding to mucosal HEV. Such tissue specificity of inhibition suggests that MEL- 14 and Hermes-3 block the function of specific lymphocyte recognition elements for lymph node and mucosal HEV, respectively. Recognition of synovial HEV also involves the 85-95-kD Hermes-1 antigen, in that a polyclonal antiserum produced against the isolated antigen blocks all three classes of lymphocyte-HEV interaction. From these studies, it is likely that the Hermes-1-defined 85-95-kD glycoprotein class either comprises a family of related but functionally independent receptors for HEV, or associates both physically and functionally with such receptors. The findings imply that related molecular mechanisms are involved in several functionally independent cell-cell recognition events that direct lymphocyte traffic.