淋巴瘤选择性抗体Lym-1识别HLA-DR10轻链上的一个不连续表位。

Lymphoma-selective antibody Lym-1 recognizes a discontinuous epitope on the light chain of HLA-DR10.

作者信息

Rose L M, Gunasekera A H, DeNardo S J, DeNardo G L, Meares C F

机构信息

Department of Chemistry, University of California 95616, USA.

出版信息

Cancer Immunol Immunother. 1996 Sep;43(1):26-30. doi: 10.1007/s002620050299.

DOI:10.1007/s002620050299

PMID:8917632

Abstract

The selectivity of Lym-1 for malignant B lymphocytes makes this monoclonal antibody a promising candidate for the delivery of toxic agents to malignant B cells. The original immunogen used for the development of Lym-1 was Raji Burkitt's lymphoma cell nuclei [Epstein A. L., Marder R. J., Winter J. N., Stathopoulos E., Chen F. M., Parker J. W., Taylor C. R. (1987) Cancer Res 47: 830]. The Lym-1 antigen was characterized at that time as a polymorphic HLA-DR variant. We prepared an affinity column using immobilized Lym-1 to isolate the Lym-1 antigen from Raji cell lysate. Immunological characterization of the immunoaffinity-purified Lym-1 antigen on Western blots led to the conclusion that the antigen is the beta chain of HLA-DR10. This was confirmed by Edman sequencing of the isolated polypeptide chain. Western blots further show that the Lym-1 epitope is only recognized if the beta chain disulfide bonds are intact. These results imply that Lym-1 binds a discontinuous epitope on the beta chain of HLA-DR10.

摘要

Lym-1 对恶性 B 淋巴细胞的选择性使得这种单克隆抗体成为将毒性药物递送至恶性 B 细胞的有前景的候选物。用于开发 Lym-1 的原始免疫原是拉吉（Raji）伯基特淋巴瘤细胞核[爱泼斯坦 A.L.，马德 R.J.，温特 J.N.，斯塔索普洛斯 E.，陈 F.M.，帕克 J.W.，泰勒 C.R.（1987 年）《癌症研究》47: 830]。当时，Lym-1 抗原被表征为一种多态性 HLA-DR 变体。我们使用固定化的 Lym-1 制备了亲和柱，以从拉吉细胞裂解物中分离 Lym-1 抗原。对免疫亲和纯化的 Lym-1 抗原进行 Western 印迹免疫表征得出结论，该抗原是 HLA-DR10 的β链。对分离的多肽链进行埃德曼测序证实了这一点。Western 印迹进一步表明，仅当β链二硫键完整时，Lym-1 表位才会被识别。这些结果表明，Lym-1 结合 HLA-DR10β链上的一个不连续表位。