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Role of tumor-associated, phosphorylated glycoprotein-membrane-antigen in bovine leukemia virus-induced lymphosarcoma.

肿瘤相关磷酸化糖蛋白膜抗原在牛白血病病毒诱导的淋巴肉瘤中的作用。

基本信息

批准号：
05404016
负责人：
OKADA Kosuke
金额：
$ 16.7万
依托单位：
Iwate University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1996
项目状态：
已结题

项目摘要

Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis (EBL), which is the most common neoplastic disease of cattle. To clarify the way in which BLV-infected cattle progress from the asymptomatic stage to the lymphoma stage, we produced a monoclonal antibody (Mab) c143 which recognized a tumor-associated antigen (TAA) that is phosphorylated in the transformed state of BLV-infected B-lymphoid cells. The TAA was mainly expressed on B-cells, macrophages, reticular cells, and a minor population of BoCD4-positive T-cells in BLV-free normal cattle. Since the nature of c143 TAA was likely to be that of the major histocompatibility complex (MHC) class II antigens, we isolated cDNAs for bovine MHC (BoLA) class alpha-chains (36-37 kD) and beta-chains (32 and 34 kD), produced transfectants that expressed a single type of BoLA class II molecules and analyzed them by flow cytometry with c143 Mab. The c143 Mab recognized the transfectant expressing BoLA-DR but not BoLA-DQ.However, the treatment of lymphocytes with c143 or anti-BoLA-DR Mab induced different effects. Although mixed lymphocyte reaction (MLR) was inhibited by the addition of anti-BoLA-DR Mab, the c143 Mab did not inhibit a proliferative response of T cells in MLR.Increased spontaneous proliferation of lymphocytes in healthy donors was obtained in the presence of c143 Mab but not anti-BoLA-DR Mab, and was much in lymphocytes from the carrier. More over, the patterns of immunohistological staining for c143 Mab in BLV-infected sheep showed distinguishing differences from those of anti-BoLA-DR Mabs.An immunohistochemical examination using c143 Mab as tumor marker for identification of EBL indicated that the bovine leukemia virus-transformed lymphocytes or neoplastic cells in peripheral blood accumulate in the marginal sinus area at the earliest stages, and subsequently proliferate and infiltrate into follicles, leading to the development of clinical signs of lymphosarcoma.

牛白血病病毒（BLV）与牛地方性白血病（EBL）有关，EBL是牛最常见的肿瘤性疾病。为了阐明BLV感染的牛从无症状阶段进展到淋巴瘤阶段的方式，我们生产了一种单克隆抗体（Mab）c143，该抗体可识别在BLV感染的B淋巴细胞转化状态下磷酸化的肿瘤相关抗原（TAA）。在无BLV的正常牛中，TAA主要在B细胞、巨噬细胞、网状细胞和少量BoCD 4阳性T细胞上表达。由于c143 TAA的性质很可能是主要组织相容性复合体（MHC）II类抗原，我们分离了牛MHC（BoLA）α链（36-37 kD）和β链（32和34 kD）的cDNA，产生了表达单一类型BoLA II类分子的转染子，并用c143 Mab通过流式细胞术对其进行了分析。c143单克隆抗体识别表达BoLA-DR的转染细胞，而不识别BoLA-DQ，但c143单克隆抗体和抗BoLA-DR单克隆抗体对淋巴细胞的作用不同。尽管加入抗BoLA-DR单抗可抑制混合淋巴细胞反应（MLR），但c143单抗并不抑制MLR中T细胞的增殖反应，在健康人中，c143单抗可引起淋巴细胞自发增殖反应的增加，而抗BoLA-DR单抗则无此作用，且携带者淋巴细胞的自发增殖反应更强。用c143单克隆抗体作为肿瘤标志物鉴定EBL的免疫组化结果表明，BLV感染绵羊外周血中牛白血病病毒转化的淋巴细胞或肿瘤细胞在最早期聚集于边缘窦区，随后增殖并浸润到滤泡中，导致淋巴肉瘤的临床症状的发展。