Detection of protein on BTLAlow cells and in vivo antibody-mediated down-modulation of BTLA on lymphoid and myeloid cells of C57BL/6 and BALB/c BTLA allelic variants
Detection of protein on BTLAlow cells and in vivo antibody-mediated down-modulation of BTLA on lymphoid and myeloid cells of C57BL/6 and BALB/c BTLA allelic variants
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DOI：
10.1016/j.imbio.2009.09.008
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发表时间：
2010-07-01
期刊：
影响因子：
2.8
通讯作者：
Rodriguez-Barbosa, Jose-Ignacio
中科院分区：
文献类型：
--
作者：
del Rio, Maria-Luisa;Kaye, Jonathan;Rodriguez-Barbosa, Jose-Ignacio
B-和T-淋巴细胞衰减因子（BTLA，CD 272）是属于IG超家族（SF）的多态性分子，其衰减BCR和TCR介导的信号传导，从而作为淋巴细胞活化的负调节剂发挥作用。在此，我们报告了一种抗小鼠BTLA mAb，（克隆4G 12 b），其显著检测BTLA（低）细胞如初始CD 4（+）细胞、CD 8（+）T细胞、树突细胞（DC）上以及NKT细胞中的蛋白表达，并且首次，我们发现在C57 BL/6（B6）和BALB/cBTLA等位基因变体中，非TNK细胞的DX 5（暗）和DX 5（亮）亚群上BTLA表达。抗-BTLA 4G 12 b mAb结合至与抗-BTLA 6A 6 mAb识别的表位重叠的表位，但与广泛接受的阻断6A 6 mAb活性的概念相反，令人惊讶的是，4G 12 b和6A 6 mAb均不阻碍鼠HVEM-mIgG（2a）.Fc重组融合蛋白与表达BTLA的细胞相互作用。最后，体内施用抗BTLA 4G 12 b mAb诱导BTLA表达的深刻且持久的下调，其导致BTLA受体内化，具有在B6和BALB/c小鼠品系的免疫应答过程期间的任何阶段关闭BTLA表达的潜在效用。(C)2009年Elsevier GmbH。All rights reserved.
B- and T-Iymphocyte attenuator (BTLA, CD272) is a polymorphic molecule belonging to the Ig superfamily (SF) that attenuates BCR and TCR-mediated signaling, and thereby functions as a negative regulator of lymphocyte activation. Herein, we report an anti-murine BTLA mAb (clone 4G12b) that remarkably detects protein expression on BTLA(low) cells such as naive CD4(+) cells, CD8(+) T cells, dendritic cells (DC), as well as in NKT cells and for the first time, we found BTLA expression on DX5(dim) and DX5(bright) subsets of non-T NK cells in both C57BL/6 (B6) and BALB/c BTLA allelic variants. Anti-BTLA 4G12b mAb binds to an overlapping epitope to that recognized by anti-BTLA 6A6 mAb, but in contrast to the concept widely accepted of blocking activity of 6A6 mAb, surprisingly neither 4G12b nor 6A6 mAbs impeded murine HVEM-mIgG(2a).Fc recombinant fusion protein from interacting with BTLA-expressing cells. Lastly, in vivo administration of anti-BTLA 4G12b mAb induced a profound and lasting down-modulation of BTLA expression that led to BTLA receptor internalization with the potential utility of shutting down BTLA expression at any stage during the course of the immune response in both B6 and BALB/c strains of mice. (C) 2009 Elsevier GmbH. All rights reserved.