Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients.
Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients.
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发表时间：
1994-06
期刊：
影响因子：
11.2
通讯作者：
Y. Kotera;Fontenot Jd;G. Pecher;Metzgar Rs;O. Finn
中科院分区：
文献类型：
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作者：
Y. Kotera;Fontenot Jd;G. Pecher;Metzgar Rs;O. Finn
在固相酶联免疫吸附测定中，使用60、80和105个残基长的合成肽（对应于人粘蛋白MUC-1蛋白核心的3、4和5.25个串联重复）作为抗原，我们筛选了来自24名乳腺癌患者、10名结肠癌患者和12名胰腺癌患者的不同疾病阶段的血清，粘蛋白特异性抗体的存在105个残基的肽是上级的允许检测高水平的抗粘蛋白抗体在每个癌症组的10.9%的血清。另外4.3%显示中间反应性。用80个残基的肽实现了较低水平的检测，并且用60个残基的肽没有检测到特异性反应性。当用纯化的全粘蛋白或短合成肽进行该测定时，抗粘蛋白抗体先前是检测不到的。抗体的存在或不存在与循环粘蛋白水平或疾病阶段无关。一个高反应性血清样品用于更精确地鉴定反应性所针对的长合成肽上的表位。该血清对105-残基肽特异的反应性被来自含有先前鉴定的免疫原性表位APDTRP的20-残基串联重复序列的NH 2-末端区域的9-残基肽阻断。另一个9-残基粘蛋白肽，从COOH-末端区域的串联重复不包含APDTRP表位，没有影响。所有的粘蛋白特异性反应被认为是IgM同种型，表明辅助T细胞的独立反应，不寻常的抗体对肽表位，但并不意外串联重复表位。
Using synthetic peptides 60,80, and 105 residues long, corresponding to 3, 4, and 5.25 tandem repeats of human mucin MUC-1 protein core, as antigens in a solid-phase enzyme-linked immunosorbent assay, we screened sera from 24 breast cancer patients, 10 colon cancer patients, and 12 pancreatic cancer patients, at various stages of disease, for the presence of mucin-specific antibodies. The 105-residue peptide was superior in allowing detection of high levels of anti-mucin antibodies in 10.9% of sera in each cancer group. Another 4.3% showed intermediate reactivity. Lower levels of detection were achieved with the 80-residue peptide, and no specific reactivity was detectable with the 60-residue peptide. Anti-mucin antibodies were previously undetectable when this assay was performed with purified whole mucin or short synthetic peptides. The presence or absence of antibody did not correlate with the levels of circulating mucin or stage of disease. One highly reactive serum sample was used to identify more precisely the epitope on the long synthetic peptide to which the reactivity was directed. The reactivity of this serum specific for the 105-residue peptide was blocked by a 9-residue peptide from the NH2-terminal region of the 20-residue tandem repeat containing the previously identified immunogenic epitope APDTRP. Another 9-residue mucin peptide, from the COOH-terminal region of the tandem repeat which does not contain the APDTRP epitope, had no effect. All the mucin-specific reactivity was found to be of the IgM isotype, indicating a helper T-cell-independent response, unusual for an antibody against a peptide epitope, but not unexpected for tandemly repeated epitopes.