Jäger E, Ringhoffer M, Arand M, Karbach J, Jäger D, Ilsemann C, Hagedorn M, Oesch F, Knuth A
II Medizinische Klinik, Krankenhaus Nordwest, Frankfurt, Germany.
Melanoma Res. 1996 Dec;6(6):419-25. doi: 10.1097/00008390-199612000-00003.
Antigenic peptides derived from several differentiation antigens of the melanocyte lineage were recently identified in human melanomas as targets for HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs). To examine their potential role in tumour-directed immune responses in vivo, we determined CTL reactivity against seven antigenic peptides derived from the Melan A/MART-1, tyrosinase and gp100/Pmel17 antigens in the peripheral blood of 10 HLA-A2+ healthy controls and 26 HLA-A2+ melanoma patients. The influenza matrix peptide (GILGFVFTL) presented by HLA-A2.1 was used as a control peptide. CTL reactivity was assessed in a mixed lymphocyte 'peptide' culture assay. Reactivity against Melan A/MART-1-derived peptide antigens was readily detectable in both melanoma patients and controls. Reactivity directed against tyrosinase-derived peptide antigens was also detected in both melanoma patients and healthy individuals, but less frequently. A measurable response against gp100/Pmel17-derived antigens was found in 1/10 controls and in 1/26 of the melanoma patients. Reactivity against the influenza matrix peptide was common in both melanoma patients and controls. Our findings show that precursor CTLs against melanocyte differentiation antigens can be detected in peripheral blood of melanoma patients and healthy individuals. The pattern of CTL reactivity directed against melanoma-associated antigens does not seem to be altered in melanoma patients. Despite antigen-specific CTL reactivity, tumour growth was not prevented in melanoma patients and autoimmune phenomena were not detected in healthy individuals. It remains to be determined whether precursor CTLs recognizing melanocyte differentiation antigens can be activated by immunization and lead to effective tumour rejection in vivo.
最近在人类黑色素瘤中发现，源自黑色素细胞谱系几种分化抗原的抗原肽是HLA - A2.1限制性细胞毒性T淋巴细胞（CTL）的靶标。为了研究它们在体内肿瘤定向免疫反应中的潜在作用，我们测定了10名HLA - A2 +健康对照者和26名HLA - A2 +黑色素瘤患者外周血中针对源自Melan A/MART - 1、酪氨酸酶和gp100/Pmel17抗原的7种抗原肽的CTL反应性。由HLA - A2.1呈递的流感病毒基质肽（GILGFVFTL）用作对照肽。在混合淋巴细胞“肽”培养试验中评估CTL反应性。在黑色素瘤患者和对照者中均易于检测到针对Melan A/MART - 1衍生肽抗原的反应性。在黑色素瘤患者和健康个体中也检测到针对酪氨酸酶衍生肽抗原的反应性，但频率较低。在1/10的对照者和1/26的黑色素瘤患者中发现了针对gp100/Pmel17衍生抗原的可测量反应。在黑色素瘤患者和对照者中针对流感病毒基质肽的反应性都很常见。我们的研究结果表明，在黑色素瘤患者和健康个体的外周血中可以检测到针对黑色素细胞分化抗原的前体CTL。针对黑色素瘤相关抗原的CTL反应性模式在黑色素瘤患者中似乎没有改变。尽管存在抗原特异性CTL反应性，但黑色素瘤患者的肿瘤生长并未得到阻止，且在健康个体中未检测到自身免疫现象。识别黑色素细胞分化抗原的前体CTL是否可以通过免疫激活并在体内导致有效的肿瘤排斥，仍有待确定。
