Immunological and molecular biological analyzes of cell surface antigens associated with T cell activation and function

自身免疫性疾病是由自身反应性免疫反应引起的自我组织破坏引起的，这在正常人和矿工中是不存在的。我们分析了倾向于自身免疫的MRL/LPR小鼠的免疫异常，特别是在[MRL/LPR-&GT；MRL/+]骨髓嵌合体中观察到的移植物抗宿主病(GVHD)样疾病。在这些研究中，已经建立了两个有趣的与白细胞反应的单抗(25T3和F6C7)。25T3单抗(IgM，k)是T细胞的特异性抗体，能与70-80%的外周CD8~+T细胞和30%的外周CD_4~+T细胞反应。经抗CD3单抗体外刺激后，25T3^+CD4^+T细胞比25T3^-CD4^+T细胞分泌更多IL-2，25T3^-CD4^+T细胞分泌IL-4比25T3^+CD4^+T细胞更多。因此，25T3mAb可将CD4^+T细胞分为Th1和Th2亚群。25T3反应性抗原约为70 kDa。F6C7mAb(IgG2b，k)与自体MLR和…激活的原始T细胞发生强烈反应更多的是MRL/LPR小鼠的原始T细胞。F6C7反应性抗原是一种约78 kDa和70 kDa的异源二聚体。虽然这些抗原不是克隆的，但这些单抗可用于分析免疫疾病中的T细胞异常。我们进一步从FGS或(NZW X BXSB)F1小鼠中建立了致肾炎的单抗，这些小鼠自发发展为肾小球肾炎。当单抗移植到SCID小鼠体内时，小鼠出现蛋白尿和肾小球肾炎。FG1H5单抗(IgM，k)与单链DNA和肾小球(主要是系膜)反应，并在肾小球沉积。FG1H5反应性抗原约为28 kDa。W/B4A9单抗(IgM，k)沿肾脏、心脏等全身毛细血管壁沉积，可与约25 kDa的血浆蛋白结合。W/B2A4单抗(IgG3，k)是一种冷球蛋白，主要沉积在肾小球毛细血管壁，并诱导高水平的蛋白尿。这些导致肾炎的单抗可能阐明导致肾炎的抗原，并有助于了解肾小球肾炎的发生机制。较少

Autoimmune diseases result from self-tissue destruction caused by auto-reactive immune responses which are not elicited in normal human and mine. We have analyzed immunological abnormalities in autoimmune-prone MRL/lpr mice, particularly graft-versus-host disease (GVHD) -like disorders obeserved in [MRL/lpr -> MRL/+] bone marrow chimeras. In these studies, two interesting monoclonal autoantibodies (25T3 and F6C7) reactive with white blood cells have been established. 25T3 monoclonal antibody (mAb) (IgM,k) is specific for T cells, and reacts to 70-80% peripheral CD8^+ T cells and 30% peripheral CD4^+ T cells. 25T3^+CD4^+T cells secret more IL-2 than 25T3^-CD4^+T cels, and 25T3^-CD4^+T cells secret more IL-4 than 25T3^+CD4^+T cells after in vitro stimulation with anti-CD3 mAb. Therefore, 25T3 mAb may divide CD4^+T cells into Th1 and Th2 subpopulaitons. The 25T3-reactive antigen is approximately 70 kDa. F6C7 mAb (IgG2b, k) strongly reacts to blastic T cells activated by autologous MLR and … More some blastic T cells of MRL/lpr mice. The F6C7-reactive antigen is a heterodimer of approximately 78 and 70 kDa. Although these antigens are not cloned, these mAbs are usuful for analyzing T cell abnormalities in immunological disorders. We have further established nephritogenic mAbs from FGS or (NZW X BXSB) F1 mice which spontaneously develop glomerulonephritis. When the mAbs are transplanted into SCID mice, the mice show proteinuria and glomerulonephritis. FG1H5 mAb (IgM,k) reacts both ssDNA and glomerulus (mainly mesangium), and deposits in the glomeruli. The FG1H5 reactive antigen is approximately 28 kDa. W/B4A9 mAb (IgM,k) deposits along systemic capillary walls in cluding kidney, heart and etc. The mAb reacts to approximately 25 kDa plasma protein. W/B2A4 mAb (IgG3, k) is a cryoglobulin, deposits mainly in glomerular capillary walls and induced high level of proteinuria. These nephritogenic mAbs may elucidate the nephritogenic antigens and contribute to understanding the mechanisms underlying the development of glomerulonephritis. Less