Krämer Björn F, Schoor Oliver, Krüger Tobias, Reichle Christian, Müller Margret, Weinschenk Toni, Hennenlotter Jörg, Stenzl Arnulf, Rammensee Hans-Georg, Stevanovic Stefan
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.
Cancer Biol Ther. 2005 Sep;4(9):943-8. doi: 10.4161/cbt.4.9.1907. Epub 2005 Sep 8.
MAGE derived HLA ligands have repeatedly been shown to elicit T-cell responses against tumor cells. In renal cell carcinoma (RCC), however, only few T-cell epitopes from cancer testis antigens have been described. To identify potential candidates, we applied a combined approach of microarray/qPCR expression analysis and sequencing of HLA ligands from RCC by mass spectrometry. We analyzed the expression of 21 MAGE genes in ten RCC samples and two glioblastoma samples and could identify the first MHC class I ligand NIGDEALIGRW from MAGED4 presented by HLA-A*25 on RCC solid tumor tissue. MAGED4 was expressed in 30% of RCC and both glioblastoma samples. Among the other MAGE family members only MAGEB2 and -C1 and the broadly expressed MAGED1, -D2, -F1 and -H1 were expressed in RCC. Ligands from MAGED4 could thus be interesting tumor-associated antigens in a subset of RCC, even though the identified ligand is presented by a rather rare allele.
黑色素瘤相关抗原（MAGE）衍生的人类白细胞抗原（HLA）配体已多次被证明能引发针对肿瘤细胞的T细胞反应。然而，在肾细胞癌（RCC）中，仅描述了少数来自癌睾丸抗原的T细胞表位。为了确定潜在的候选物，我们采用了微阵列/qPCR表达分析和通过质谱对RCC的HLA配体进行测序的联合方法。我们分析了10个RCC样本和2个胶质母细胞瘤样本中21个MAGE基因的表达，并在RCC实体瘤组织中鉴定出由HLA - A*25呈递的来自MAGED4的首个MHC I类配体NIGDEALIGRW。MAGED4在30%的RCC样本和胶质母细胞瘤样本中均有表达。在其他MAGE家族成员中，只有MAGEB2和 - C1以及广泛表达的MAGED1、 - D2、 - F1和 - H1在RCC中表达。因此，尽管鉴定出的配体由一个相当罕见的等位基因呈递，但来自MAGED4的配体在一部分RCC中可能是有趣的肿瘤相关抗原。
