Identification of epitope mimics recognized by CTL reactive to the melanoma/melanocyte-derived peptide MART-1(27-35).
Identification of epitope mimics recognized by CTL reactive to the melanoma/melanocyte-derived peptide MART-1(27-35).
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DOI：
10.1084/jem.184.2.647
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发表时间：
1996-08-01
影响因子：
15.3
通讯作者：
Rivoltini, L
中科院分区：
文献类型：
--
作者：
Loftus, DJ;Castelli, C;Clay, TM;Squarcina, P;Marincola, FM;Nishimura, MI;Parmiani, G;Appella, E;Rivoltini, L
对黑素瘤（自身）抗原MART-1/melan A的表位MART-1（27-35）的CTL反应性经常在肿瘤浸润淋巴细胞中观察到，并且可以容易地从表达HLA-A*0201的黑素瘤患者的外周血中引发。现有的数据表明，这些观察结果与其他HLA-A*0201呈递的黑色素瘤自身抗原观察到的CTL应答的规律性形成对比。基于初步发现，我们假设对MART-1的CTL应答可能部分地通过T细胞与来自MART-1以外来源的肽的接触而增强，所述肽显示出与MART-1的序列相似性（27-35）。为了测试这一想法，使用从MART-1的单取代肽类似物的效应子识别分析开发的标准进行潜在MART-1表位模拟物的蛋白质数据库搜索（27-35）。合成肽是针对一部分检索的序列制备的;测试的12/40肽能够使靶细胞对一种或多种抗MART- 1效应物的裂解敏感。所识别的肽对应于病毒、细菌和人（自身）来源的多种蛋白质中存在的序列。一种肽来源于常见病原体HSV-1的糖蛋白C;用编码天然糖蛋白C的重组牛痘病毒感染的细胞被抗MART-1效应物裂解。我们的研究结果总体上表明，符合A2.1结合基序的序列，并具有抗MART-1 CTL识别所必需的功能，经常出现在蛋白质中。这些发现进一步表明，T细胞可能在体内遇到多种这样的序列，并且表位模拟可能在调节对MART-1的CTL应答中起作用（27-35）。
CTL reactivity to the epitope MART-1(27-35), of the melanoma (self) antigen MART-1/melan A is frequently observed in tumor-infiltrating lymphocytes and may be readily elicited from the peripheral blood of melanoma patients that express HLA-A*0201. Available data suggest that these observations contrast with those made for other HLA-A*0201- presented melanoma self antigens regarding the regularity of observed CTL responses. Based on preliminary findings, we hypothesized that the CTL response to MART-1 might be augmented in part by T cell encounters with peptides derived from sources other than MART-1, which show sequence similarity to MART-1(27-35). To test this idea, a protein database search for potential MART-1 epitope mimics was done using criteria developed from analyses of effector recognition of singly- substituted peptide analogues of MART-1(27-35). Synthetic peptides were made for a portion of the sequences retrieved; 12/40 peptides tested were able to sensitize target cells for lysis by one or more anti-MART- 1 effectors. The peptides recognized correspond to sequences occurring in a variety of proteins of viral, bacterial, and human (self) origin. One peptide derives from glycoprotein C of the common pathogen HSV-1; cells infected with recombinant vaccinia virus encoding native glycoprotein C were lysed by anti-MART-1 effectors. Our results overall indicate that sequences conforming to the A2.1 binding motif and possessing features essential to recognition by anti-MART-1 CTL occur frequently in proteins. These findings further suggest that T cells might encounter a variety of such sequences in vivo, and that epitope mimicry may play a role in modulating the CTL response to MART-1(27-35).
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影响因子：
5.4
作者：
GENEVEE, C;DIU, A;HERCEND, T
通讯作者：
HERCEND, T
影响因子：
5.4
作者：
LEHMANN, F;MARCHAND, M;COULIE, PG
通讯作者：
COULIE, PG
影响因子：
32.4
作者：
BOEL, P;WILDMANN, C;VANDERBRUGGEN, P
通讯作者：
VANDERBRUGGEN, P
DOI：
10.1084/jem.178.2.489
发表时间：
1993-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brichard V;Van Pel A;Wölfel T;Wölfel C;De Plaen E;Lethé B;Coulie P;Boon T
通讯作者：
Boon T
DOI：
10.1084/jem.180.1.35
发表时间：
1994-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coulie PG;Brichard V;Van Pel A;Wölfel T;Schneider J;Traversari C;Mattei S;De Plaen E;Lurquin C;Szikora JP;Renauld JC;Boon T
通讯作者：
Boon T