Engleman E G, Benike C, Osborne B, Goldsby R
Proc Natl Acad Sci U S A. 1980 Mar;77(3):1607-11. doi: 10.1073/pnas.77.3.1607.
In animals and in man, diverse immunologic functions are mediated by specialized T-cell (thymus-derived lymphocyte) subsets that are distinguishable from one another on the basis of differences in cell surface determinants. Unfortunately, in humans, subset-specific antibodies have been difficult to generate. In this study, production of a murine monoclonal antibody specific for a subset of human T cells was achieved by fusing a sensitized B cell (bone marrow-derived cell) with a myeloma cell and isolating the antibody secreted by the resultant hybrid clone. This antibody binds 30-35% of peripheral T lymphocytes (T(a) (+) cells) but fails to bind remaining T lymphocytes (T(a) (-) cells), B lymphocytes, or monocytes. T(a) (+) and T(a) (-) subpopulations were separated with a fluorescence-activated cell sorter and their in vitro responses to various stimuli were assessed. T(a) (+) and T(a) (-) cells respond equally well to soluble antigens, allogeneic B cells, and autologous B cells, but only T(a) (+) cells respond to concanavalin A. T(a) (+) cells cultured in the presence of concanavalin A gradually lose the T(a) marker, an effect not observed after stimulation with phytohemagglutinin, soluble antigens, or alloantigens. These results suggest that the functional subpopulation of T cells defined by T(a) does not correspond to any previously described human T cell subset. Furthermore, somatic cell hybridization has been shown to be a feasible method for production of monoclonal antibodies specific for subpopulations of human lymphocytes.
在动物和人类中,多种免疫功能由特殊的T细胞(胸腺衍生淋巴细胞)亚群介导,这些亚群可根据细胞表面决定簇的差异相互区分。不幸的是,在人类中,很难产生亚群特异性抗体。在本研究中,通过将致敏的B细胞(骨髓衍生细胞)与骨髓瘤细胞融合,并分离所得杂交克隆分泌的抗体,获得了一种针对人类T细胞亚群的鼠单克隆抗体。该抗体可结合30%-35%的外周T淋巴细胞(T(a)(+)细胞),但不结合其余的T淋巴细胞(T(a)(-)细胞)、B淋巴细胞或单核细胞。用荧光激活细胞分选仪分离T(a)(+)和T(a)(-)亚群,并评估它们对各种刺激的体外反应。T(a)(+)和T(a)(-)细胞对可溶性抗原、同种异体B细胞和自体B细胞的反应同样良好,但只有T(a)(+)细胞对刀豆球蛋白A有反应。在刀豆球蛋白A存在下培养的T(a)(+)细胞逐渐失去T(a)标记,在用植物血凝素、可溶性抗原或同种异体抗原刺激后未观察到这种效应。这些结果表明,由T(a)定义的T细胞功能亚群与任何先前描述的人类T细胞亚群均不对应。此外,体细胞杂交已被证明是生产针对人类淋巴细胞亚群的单克隆抗体的可行方法。