Steinberger Peter, Majdic Otto, Derdak Sophia V, Pfistershammer Katharina, Kirchberger Stefanie, Klauser Christoph, Zlabinger Gerhard, Pickl Winfried F, Stöckl Johannes, Knapp Walter
Institute of Immunology, University of Vienna Medical School, Vienna, Austria.
J Immunol. 2004 Feb 15;172(4):2352-9. doi: 10.4049/jimmunol.172.4.2352.
In an effort to characterize molecules with immunoregulatory potential, we raised mAbs to human dendritic cells. We selected an Ab that recognizes a molecule that is induced on monocytes differentiated in vitro toward dendritic cells. Retroviral expression cloning identified this molecule as B7-H3, a member of the B7 family described recently. In contrast to an earlier report, in which B7-H3 was described as a molecule consisting of two Ig-like domains, our cDNA encoded a type I membrane protein with four Ig-like domains, and the molecule identified by us was therefore named 4Ig-B7-H3. mRNA analysis as well as Western blotting experiments performed by us did not reveal evidence for a small B7-H3. B7-H3 is not expressed on peripheral blood lymphocytes, monocytes, or granulocytes. Upon in vitro stimulation, the expression of B7-H3 is induced on T cells, B cells, and NK cells. A number of different approaches were used to investigate the function of human B7-H3. In contrast to an earlier report, our data do not support a costimulatory role of B7-H3 in anti-CD3-mediated activation of the TCR-complex resulting in T cell proliferation and IFN-gamma production.
为了鉴定具有免疫调节潜能的分子，我们制备了针对人树突状细胞的单克隆抗体。我们筛选出一种能识别在体外分化为树突状细胞的单核细胞上诱导产生的分子的抗体。逆转录病毒表达克隆鉴定该分子为B7-H3，它是最近描述的B7家族的一员。与之前将B7-H3描述为由两个免疫球蛋白样结构域组成的分子的报道不同，我们的cDNA编码一种具有四个免疫球蛋白样结构域的I型膜蛋白，因此我们鉴定的该分子被命名为4Ig-B7-H3。我们进行的mRNA分析以及蛋白质免疫印迹实验均未发现存在小B7-H3的证据。外周血淋巴细胞、单核细胞或粒细胞上均不表达B7-H3。在体外刺激后，T细胞、B细胞和NK细胞上会诱导B7-H3的表达。我们采用了多种不同方法来研究人B7-H3的功能。与之前的报道不同，我们的数据不支持B7-H3在抗CD3介导的TCR复合物激活中发挥共刺激作用从而导致T细胞增殖和产生γ干扰素。
