INHIBITION OF MURINE T-CELL-MEDIATED CYTOLYSIS AND T-CELL PROLIFERATION BY A RAT MONOCLONAL-ANTIBODY IMMUNOPRECIPITATING 2 LYMPHOID-CELL SURFACE POLYPEPTIDES OF 94000 AND 180000 MOLECULAR-WEIGHT

INHIBITION OF MURINE T-CELL-MEDIATED CYTOLYSIS AND T-CELL PROLIFERATION BY A RAT MONOCLONAL-ANTIBODY IMMUNOPRECIPITATING 2 LYMPHOID-CELL SURFACE POLYPEPTIDES OF 94000 AND 180000 MOLECULAR-WEIGHT
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DOI:
10.1002/eji.1830120112
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发表时间:
1982-01-01
影响因子:
5.4
通讯作者:
GOLSTEIN, P
GOLSTEIN, P
中科院分区:
医学3区
文献类型:
--
作者:
PIERRES, M;GORIDIS, C;GOLSTEIN, P

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单克隆抗体方法被用于鉴定参与T细胞功能的膜结构。为了优化产生和检测相关抗体的机会,采用了异种致敏方案,并基于功能而非结构的依据对杂交瘤上清液进行筛选,以检测其抑制特定功能的能力。检测的功能是T细胞介导的细胞溶解。利用小鼠溶细胞性抗同种异体细胞群对大鼠进行致敏,将其脾细胞融合以产生杂交瘤;对后者的上清液进行筛选,以检测其在体外抑制小鼠T细胞介导的细胞溶解的能力。获得了几种抑制性抗体,其中一种,H35 - 89.9单克隆抗体,得到了更详细的研究。它通过作用于效应细胞,抑制T细胞的特异性以及伴刀豆球蛋白A(Con A)介导的细胞溶解。在白细胞介素2产生之后,它通过作用于反应细胞,可逆地抑制可溶性抗原、同种抗原和Con A诱导的T细胞增殖(但不抑制脂多糖(LPS)诱导的B细胞增殖)。它还对Con A和LPS诱导的母细胞以及[小鼠白血病]EL4细胞有解聚作用。它从胸腺细胞膜制剂中免疫沉淀出两种表观分子量分别为94,000和180,000的结构,并识别T和B淋巴细胞上的细胞表面决定簇。几种针对不同效应细胞膜结构的抗体可能抑制细胞溶解。H35 - 89.9单克隆抗体的情况,它具有多种功能效应并免疫沉淀两种膜多肽,引发了这些结构和功能之间各种可能关系的问题。
The monoclonal antibody methodology was used to identify membrane structures involved in T cell functions. To optimize chances to produce and detect relevant antibodies, a xenogeneic sensitization protocol was utilized and hybridoma supernatants were screened, on functional rather than structural grounds, for their ability to inhibit a given function. The test function was T cell-mediated cytolysis. Mouse cytolytic anti-allogeneic cell populations were used to sensitize a rat, the spleen cells of which were fused to produce hybridomas; the supernatants of the latter were screened for their ability to inhibit mouse T cell-mediated cytolysis in vitro. Several inhibitory antibodies were obtained, one of which, H35-89.9 monoclonal antibody, was studied in more detail. It inhibited specific and concanavalin A (Con A)-mediated cytolysis by T cells, by acting on the effector cells. It reversibly inhibited soluble antigen-, alloantigen and Con A-induced T cell proliferation (but not LPS[lipopolysaccharide]-induced B cell proliferation), after the production of interleukin 2, by acting on the responder cells. It also had a desagglutinating effect on Con A and LPS blasts and on [mouse leukemia] EL4 cells. It immunoprecipitated from thymocyte membrane preparations 2 structures of 94,000 and 180,000 apparent MW, and recognized cell surface determinants on both T and B lymphocytes. Several antibodies directed against distinct effector cell membrane structures probably inhibit cytolysis. The case of H35-89.9 monoclonal antibody, which exerts multiple functional effects and immunoprecipitates 2 membrane polypeptides, raises the problem of the various possible relationships between these structures and functions.