A peptide encoded by the human MAGE3 gene and presented by HLA-B44 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE3
A peptide encoded by the human MAGE3 gene and presented by HLA-B44 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE3
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DOI：
10.1007/s002510050078
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发表时间：
1996-01-01
期刊：
影响因子：
3.2
通讯作者：
Coulie, PG
中科院分区：
文献类型：
--
作者：
Herman, J;vanderBruggen, P;Coulie, PG
人MAGE 3基因在各种组织学类型的肿瘤中表达的比例很大，但在睾丸和胎盘以外的正常成人组织中沉默。因此，MAGE 3编码的抗原可能是特异性抗肿瘤免疫的有用靶标。MAGE 3基因编码的两种抗原肽先前已被报道。一种是由HLA-A1呈递给溶细胞性T淋巴细胞（CTL），另一种是由HLA-A2分子呈递。合成了含有HLA-B_（44）肽结合基序的MAGE_3肽，用与HLA-B_（44）结合最强的MAGE_3肽MEVDPIGHLY刺激正常人外周血T淋巴细胞。获得了不仅识别用肽致敏的HLA-B44细胞，而且识别表达MAGE 3的HLA-B44肿瘤细胞系的CTL克隆。在高加索人群中，表达MAGE 3/HLA-B44抗原的转移性黑色素瘤的比例应达到约17%，因为24%的个体携带HLA-B44等位基因，并且这些肿瘤中的76%表达MAGE 3。
The human MAGE3 gene is expressed in a significant proportion of tumors of various histological types, but is silent in normal adult tissues other than testis and placenta. Antigens encoded by MAGE3 may therefore be useful targets for specific antitumor immunization. Two antigenic peptides encoded by the MAGE3 gene have been reported previously. One is presented to cytolytic T lymphocytes (CTL) by HLA-A1, the other by HLA-A2 molecules, Here we show that MAGE3 also codes for a peptide that is presented to CTL by HLA-B44. MAGE3 peptides containing the HLA-B44 peptide binding motif were synthesized, Peptide MEVDPIGHLY, which showed the strongest binding to HLA-844, was used to stimulate blood T lymphocytes from normal HLA-B44 donors. CTL clones were obtained that recognized not only HLA-B44 cells sensitized with the peptide, but also HLA-B44 tumor cell lines expressing MAGE3. The proportion of metastatic melanomas expressing the MAGE3/HLA-B44 antigen should amount to approximately 17% in the Caucasian population, since 24% of individuals carry the HLA-B44 allele and 76% of these tumors express MAGE3.