Characterization of antigenic peptides presented by HLA‐B44 molecules on tumor cells expressing the gene MAGE‐3

Characterization of antigenic peptides presented by HLA‐B44 molecules on tumor cells expressing the gene MAGE‐3
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表达 MAGE-3 基因的肿瘤细胞上 HLA-B44 分子呈递的抗原肽的表征

DOI:
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发表时间:
1996
影响因子:
6.4
通讯作者:
C. Traversari
C. Traversari
中科院分区:
医学1区
文献类型:
--
作者:
K. Fleischhauer;D. Fruci;P. van Endert;J. Herman;S. Tanzarella;H. Wallny;P. Coulie;C. Bordignon;C. Traversari

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从 MAGE-3 基因编码的蛋白质的氨基酸序列中筛选出含有 HLA-B44 结合基序的肽。合成了九种肽,并在 HLA I 类 α 链重折叠测定中分析了它们与 HLA-B*4402 和 -B*4403 的结合亲和力。选择对 HLA-B*4403 具有结合亲和力的四种肽进行体外细胞毒性 T 淋巴细胞诱导测定,使用来自健康 B*4403+ 供体的肽脉冲、自体活化 B 淋巴母细胞作为抗原呈递细胞。肽特异性效应子只能针对一种肽 M3-167 产生。该肽特异的细胞毒性 T 淋巴细胞也能够识别表达 HLA-B44 和基因 MAGE-3 的黑色素瘤细胞系,强烈表明 M3-167 是 HLA-B44 呈递的自然加工的 MAGE-3 编码表位。M3-167 是 M3-168 的 1 个氨基酸 N 端延伸,M3-168 是 HLA-A1 呈递的自然加工的表位 MAGE-3 编码的表位,前面已经描述过。这 2 种肽的 TAP 结合研究表明,M3-167 的 TAP 亲和力比 M3-168 高约 9 倍。 M3-167 或更长的前体可以被转运到内质网,在那里它可以被修剪以供 HLA-A1 或 -B44 分子呈递。综上所述,我们的数据表明 M3-167 可能是由 MAGE-3 基因编码的免疫显性肽。 © 1996 Wiley-Liss, Inc.
The amino acid sequence of the protein encoded by the gene MAGE‐3was screened for peptides containing the binding motif for HLA‐B44. Nine peptides were synthesized, and their binding affinity for HLA‐B*4402 and ‐B*4403 was analyzed in an HLA class I α‐chain refolding assay. Four peptides with binding affinity for HLA‐B*4403 were chosen for in vitro cytotoxic T‐lymphocyte induction assays using as antigen‐presenting cells peptide‐pulsed, autologous activated B lymphoblasts from a healthy, B*4403+ donor. Peptide‐specific effectors could be raised only against one peptide, M3‐167. Cytotoxic T lymphocytes specific for this peptide were also able to recognize melanoma cell lines expressing HLA‐B44 and the gene MAGE‐3, strongly suggesting that M3‐167is a naturally processed MAGE‐3‐encoded epitope presented by HLA‐B44.M3‐167 is a 1 amino acid N‐terminal extension of M3‐168, a naturally processed epitope MAGE‐3‐encoded epitope presented by HLA‐A1 that has been previously described. TAP binding studies of these 2 peptides revealed that the TAP affinity of M3‐167 is about 9‐fold higher than that of M3‐168. M3‐167 or a longer precursor could be transported into the endoplasmatic reticulum, where it could be trimmed for presentation by HLA‐A1 or ‐B44 molecules. Taken together, our data suggest that M3‐167 could be an immunodominant peptide encoded by the gene MAGE‐3. © 1996 Wiley‐Liss, Inc.
DOI: 10.1016/1074-7613(95)90159-0
发表时间: 1995-07-01
期刊: IMMUNITY
影响因子: 32.4
作者:
TUSSEY, LG;ROWLANDJONES, S;MCMICHAEL, AJ
通讯作者: MCMICHAEL, AJ
DOI: 10.1073/pnas.91.6.2105
发表时间: 1994-03-15
影响因子: 11.1
作者:
CELIS, E;TSAI, V;SERRA, HM
通讯作者: SERRA, HM
DOI: 10.1016/0022-2836(91)90567-p
发表时间: 1991-05-20
影响因子: 5.6
作者:
SAPER, MA;BJORKMAN, PJ;WILEY, DC
通讯作者: WILEY, DC