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

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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.