The immunopeptidomes of two transmissible cancers and their host have a common, dominant peptide motif.
The immunopeptidomes of two transmissible cancers and their host have a common, dominant peptide motif.
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两种传染性癌症及其宿主的免疫肽段具有共同的显性肽基序。
DOI：
10.1111/imm.13307
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发表时间：
2021-06
期刊：
影响因子：
6.4
通讯作者：
Siddle HV
中科院分区：
文献类型：
--
作者：
Gastaldello A;Ramarathinam SH;Bailey A;Owen R;Turner S;Kontouli N;Elliott T;Skipp P;Purcell AW;Siddle HV
可传播癌症是一种恶性细胞，可以在人群中的个人之间传播，类似于寄生虫和可移动的移植物。现存最大的有袋食肉动物塔斯马尼亚魔鬼的生存受到了两种独立传播性癌症谱系的显著出现的威胁，即魔鬼面部肿瘤(DFT)1和魔鬼面部肿瘤2(DFT2)。为了帮助疫苗的开发和询问如何克服组织相容性障碍，我们分析了来自塔斯马尼亚魔鬼细胞和每个可传播癌症的代表性细胞系的主要组织相容性复合体I类(MHC-I)分子结合的多肽。在这里，我们表明，与成纤维细胞相比，DFT1+、干扰素-γ和DFT2细胞株表达的MHC-I同种异型受到限制，潜在地减少了多肽呈递的广度。比较来自DFT1+、干扰素γ、DFT2和宿主成纤维细胞的多肽发现，尽管不同细胞系之间的MHC-I同型不同，但多肽的主要基序是，在多肽的第3位和Ω位有疏水性亮氨酸残基。DFT1和DFT2都是来自神经蛋白的多肽，这反映了一个共同的细胞来源，可以用于疫苗设计。这些结果表明，肿瘤和宿主之间的MHC-I分子的多态可以被一个共同的多肽基序“隐藏”，这为感染细胞提供了允许通过的可能性，并展示了哺乳动物组织相容性障碍的复杂性。塔斯马尼亚魔鬼有两种独立的可传播癌症，它们在人群中传播。我们已经确定了癌症和宿主细胞系的免疫表位。我们发现癌细胞和宿主细胞系有一个共同的多肽基序。
Transmissible cancers are malignant cells that can spread between individuals of a population, akin to both a parasite and a mobile graft. The survival of the Tasmanian devil, the largest remaining marsupial carnivore, is threatened by the remarkable emergence of two independent lineages of transmissible cancer, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to major histocompatibility complex class I (MHC‐I) molecules from Tasmanian devil cells and representative cell lines of each transmissible cancer. Here, we show that DFT1 + IFN‐γ and DFT2 cell lines express a restricted repertoire of MHC‐I allotypes compared with fibroblast cells, potentially reducing the breadth of peptide presentation. Comparison of the peptidomes from DFT1 + IFNγ, DFT2 and host fibroblast cells demonstrates a dominant motif, despite differences in MHC‐I allotypes between the cell lines, with preference for a hydrophobic leucine residue at position 3 and position Ω of peptides. DFT1 and DFT2 both present peptides derived from neural proteins, which reflects a shared cellular origin that could be exploited for vaccine design. These results suggest that polymorphisms in MHC‐I molecules between tumours and host can be ‘hidden’ by a common peptide motif, providing the potential for permissive passage of infectious cells and demonstrating complexity in mammalian histocompatibility barriers. The Tasmanian devil has two independent transmissible cancers that circulate in the population. We have characterized the immunopeptidomes of both cancers and host cell line. We find that the cancers and host cell lines have a common peptide motif.
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影响因子：
64.8
作者：
Metzger MJ;Villalba A;Carballal MJ;Iglesias D;Sherry J;Reinisch C;Muttray AF;Baldwin SA;Goff SP
通讯作者：
Goff SP
DOI：
10.4049/jimmunol.1700893
发表时间：
2017-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jurtz V;Paul S;Andreatta M;Marcatili P;Peters B;Nielsen M
通讯作者：
Nielsen M
影响因子：
7.4
作者：
Bhatia, Vivek N.;Perlman, David H.;Costello, Catherine E.;McComb, Mark E.
通讯作者：
McComb, Mark E.
影响因子：
3
作者：
Kim Y;Sidney J;Pinilla C;Sette A;Peters B
通讯作者：
Peters B
影响因子：
64.5
作者：
Metzger MJ;Reinisch C;Sherry J;Goff SP
通讯作者：
Goff SP