Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes.
Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes.
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DOI：
10.1084/jem.179.3.921
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发表时间：
1994-03-01
期刊：
影响因子：
--
通讯作者：
Boon T
中科院分区：
文献类型：
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作者：
Gaugler B;Van den Eynde B;van der Bruggen P;Romero P;Gaforio JJ;De Plaen E;Lethé B;Brasseur F;Boon T
人黑色素瘤细胞系MZ2-MEL表达多种自身溶细胞T淋巴细胞(CTL)克隆识别的抗原。我们之前曾报道过一种名为MAGE-1的基因，它编码其中一种抗原MZ2-E。我们在这里表明，存在于同一肿瘤上的MZ2-D抗原是由MAGE基因家族的另一个成员MAGE-3编码的。与MAGE-1类似，MAGE-3由三个外显子组成，大的开放阅读框完全位于第三外显子。ITS序列与MAGE-1有73%的同源性。与MZ2-E一样，MZ2-D抗原是由人类白细胞抗原A1提呈的。MZ2-D的抗原肽是由MAGE-3序列编码的非肽，该序列与编码MZ2-E肽的MAGE-1序列同源。用单一Ala取代多肽进行的竞争实验表明，第3位氨基酸残基Asp和第9位Tyr残基是MAGE-1多肽与人类白细胞抗原A1结合所必需的。MAGE-3基因在黑色素瘤、头颈部鳞状细胞癌、肺癌和乳腺癌等多种类型的肿瘤中都有表达，但在除睾丸外的正常组织中不表达。它在黑色素瘤样本中的表达比例高于MAGE-1。因此，MAGE-3编码的抗原可能在黑色素瘤患者的特异性免疫治疗中具有广泛的适用性。
Human melanoma cell line MZ2-MEL expresses several antigens recognized by autologous cytolytic T lymphocyte (CTL) clones. We reported previously the identification of a gene, named MAGE-1, that codes for one of these antigens named MZ2-E. We show here that antigen MZ2-D, which is present on the same tumor, is encoded by another member of the MAGE gene family named MAGE-3. Like MAGE-1, MAGE-3 is composed of three exons and the large open reading frame is entirely located in the third exon. Its sequence shows 73% identity with MAGE-1. Like MZ2-E, antigen MZ2-D is presented by HLA-A1. The antigenic peptide of MZ2-D is a nonapeptide that is encoded by the sequence of MAGE-3 that is homologous to the MAGE-1 sequence coding for the MZ2-E peptide. Competition experiments using single Ala-substituted peptides indicated that amino acid residues Asp in position 3 and Tyr in position 9 were essential for binding of the MAGE-1 peptide to HLA-A1. Gene MAGE-3 is expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes. It is expressed in a larger proportion of melanoma samples than MAGE-1. MAGE-3 encoded antigens may therefore have a wide applicability for specific immunotherapy of melanoma patients.