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近交系小鼠化学诱导肉瘤的肿瘤排斥抗原

Tumor rejection antigens of chemically induced sarcomas of inbred mice.

作者信息

Srivastava P K, DeLeo A B, Old L J

出版信息

Proc Natl Acad Sci U S A. 1986 May;83(10):3407-11. doi: 10.1073/pnas.83.10.3407.

Abstract

Chemically induced sarcomas of inbred mice are immunogenic in syngeneic hosts, and preimmunization with tumor cells leads to resistance to subsequent tumor transplants. The tumor rejection antigens (TRAs) that mediate this reaction are highly specific for each tumor; cross-protection between different syngeneic sarcomas is rare. Isolated membrane and cytosol fractions from two antigenically distinct BALB/c sarcomas, Meth A and CMS5, have TRA activity, and biochemical characterization of the active components from the cytosol and plasma membranes of these two tumors identified a glycoprotein of Mr 96,000. Immunization with unfractionated Meth A cytosol frequently leads to tumor enhancement, but the tumor-enhancing activity (TEA) is lost on fractionation and TRA activity becomes demonstrable. As Meth A and CMS5 lack expression of murine leukemia virus (MuLV) antigens or transcripts, MuLV-related antigens cannot be involved in the TEA or TRA activities of these tumors. In contrast to the lack of cross-reactivity between Meth A and CMS5 TRAs in transplantation tests, rabbit antiserum prepared against the Meth A Mr 96,000 antigen reacted with the CMS5 Mr 96,000 antigen. In view of the biochemical and antigenic similarities of Meth A and CMS5 TRAs, we propose that structurally related but distinct Mr 96,000 glycoproteins are expressed in chemically induced sarcomas and that these molecules are responsible for the individually specific immunogenicity of these tumors.

摘要

化学诱导的近交系小鼠肉瘤在同基因宿主中具有免疫原性,用肿瘤细胞进行预免疫可导致对随后肿瘤移植产生抗性。介导这种反应的肿瘤排斥抗原(TRA)对每种肿瘤具有高度特异性;不同同基因肉瘤之间的交叉保护很少见。从两种抗原性不同的BALB/c肉瘤Meth A和CMS5中分离出的膜和胞质溶胶组分具有TRA活性,对这两种肿瘤的胞质溶胶和质膜中的活性成分进行生化表征鉴定出一种分子量为96,000的糖蛋白。用未分级的Meth A胞质溶胶进行免疫常常导致肿瘤增强,但分级分离后肿瘤增强活性(TEA)丧失,TRA活性变得可检测到。由于Meth A和CMS5缺乏鼠白血病病毒(MuLV)抗原或转录本的表达,MuLV相关抗原不可能参与这些肿瘤的TEA或TRA活性。与移植试验中Meth A和CMS5 TRA之间缺乏交叉反应性相反,针对Meth A分子量96,000抗原制备的兔抗血清与CMS5分子量96,000抗原发生反应。鉴于Meth A和CMS5 TRA的生化和抗原相似性,我们提出在化学诱导的肉瘤中表达结构相关但不同的分子量96,000糖蛋白,并且这些分子负责这些肿瘤各自特异性的免疫原性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffff/323523/66f7cf5ff11c/pnas00314-0369-a.jpg

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