BLOOD-GROUP A CROSS-REACTING EPITOPE DEFINED BY MONOCLONAL-ANTIBODIES NCC-LU-35 AND NCC-LU-81 EXPRESSED IN CANCER OF BLOOD GROUP-O OR GROUP-B INDIVIDUALS - ITS IDENTIFICATION AS TN ANTIGEN
BLOOD-GROUP A CROSS-REACTING EPITOPE DEFINED BY MONOCLONAL-ANTIBODIES NCC-LU-35 AND NCC-LU-81 EXPRESSED IN CANCER OF BLOOD GROUP-O OR GROUP-B INDIVIDUALS - ITS IDENTIFICATION AS TN ANTIGEN
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DOI：
10.1073/pnas.82.20.7039
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
HAKOMORI, S
中科院分区：
文献类型：
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作者：
HIROHASHI, S;CLAUSEN, H;HAKOMORI, S
分别用体内生长的人肺癌Lu65异种移植瘤细胞和体外培养的完整细胞的膜制品免疫小鼠，建立了两种单克隆抗体NCC-LU-35和NCC-LU-81。这两种抗体与大多数人类腺癌特异性反应，无论宿主的血型ABO状态如何，以及与正常组织和A型血个体的红细胞反应。抗原性与通过凝胶过滤Lu65肿瘤提取物分离的高分子量粘蛋白样糖蛋白相关。粘蛋白样糖蛋白的表位已被鉴定为α- N-乙酰半乳糖胺基残基直接与多肽的丝氨酸或苏氨酸残基O-糖苷连接。该表位在几年前被血清学检测到，并命名为Tn。我们对表位的鉴定基于以下结果：（i）抗原对α- N-乙酰氨基半乳糖苷酶，但不与唾液酸酶或α-岩藻糖苷酶。(ii)各种单岩藻糖基和二岩藻糖基A决定簇，1型或2型链，与两种抗体交叉反应。(iii)与两种抗体的反应性可以通过用唾液酸酶处理正常红细胞的血型糖蛋白A，然后用β-葡萄糖酸酶处理来产生。半乳糖苷酶。(iv)N-[3H]乙酰半乳糖胺可以通过半乳糖氧化酶/NaB3H4处理从Lu65粘蛋白样糖蛋白释放，但不能从正常结肠粘膜的粘蛋白样糖蛋白在还原β-半乳糖胺后释放。消除（碱性硼氢化物处理）。抗原可以是在属于所有ABO血型的宿主的多种人类腺癌中出现的肿瘤相关A交叉反应抗原之一。
Two monoclonal antibodies, NCC-LU-35 and NCC-LU-81, have been established after immunization of mice with membrane preparations of human lung cancer Lu65 tumor xenograft cells grown in vivo and intact cells cultured in vitro, respectively. These two antibodies react specifically with a majority of human adenocarcinomas, irrespective of the host''s blood group ABO status, as well as with normal tissues and erythrocytes of blood group A individuals. The antigenicity is associated with a high molecular weight mucin-like glycoprotein separated by gel filtration of Lu65 tumor extracts. The epitope of the mucin-like glycoprotein has been identified as .alpha.-N-acetylgalactosaminyl residue directly linked O-glycosidically to serine or threonine residues of polypeptides. This epitope was serologically detected several years ago and given the name Tn. Our identification of the epitope is based on the following results: (i) The antigen is sensitive to .alpha.-N-acetylgalactosaminidase, but not to sialidase or .alpha.-fucosidase. (ii) Various mono- and difucosyl A determinants, either type 1 or type 2 chain, cross-react with both antibodies. (iii) The reactivity with both antibodies can be created by treatment of glycophorin A of normal erythrocytes with sialidase followed by .beta.-galactosidase. (iv) N-[3H]acetylgalactosamine can be released by galactose oxidase/NaB3H4 treatment from the Lu65 mucin-like glycoprotein but not from the mucin-like glycoprotein of normal colonic mucosa upon reductive .beta.-elimination (alkaline borohydride treatment). The antigen may be one of the tumor-associated A cross-reacting antigens occurring in a wide variety of human adenocarcinomas of hosts belonging to all ABO blood groups.