Characterization of the Canine MHC Class I DLA-88*50101 Peptide Binding Motif as a Prerequisite for Canine T Cell Immunotherapy.
Characterization of the Canine MHC Class I DLA-88*50101 Peptide Binding Motif as a Prerequisite for Canine T Cell Immunotherapy.
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DOI：
10.1371/journal.pone.0167017
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Planz O
中科院分区：
文献类型：
--
作者：
Barth SM;Schreitmüller CM;Proehl F;Oehl K;Lumpp LM;Kowalewski DJ;Di Marco M;Sturm T;Backert L;Schuster H;Stevanović S;Rammensee HG;Planz O
使用小鼠作为人类临床开发基础的临床前环境存在局限性。在癌症中，人类和狗之间存在相似之处;因此，狗患者可以成为从小鼠模型实验室研究向人类临床试验过渡的一个环节。MHC分子上呈递的肽的知识对于开发高度特异性的基于T细胞的免疫疗法是基础。该信息可用于人MHC分子，但不存在犬MHC。在本研究中，我们的特点是狗白细胞抗原（DLA）I类等位基因DLA-88*50101的结合基序，使用人C1 R和K562转染细胞表达DLA-88*50101重链。MHC I类免疫亲和纯化揭示了3720个DLA-88*50101衍生肽，这使得能够确定主要锚位置。DLA-88*50101的特征性结合基序与HLA-A*02：01相似。通过流式细胞术对HLA-A*02：01和DLA-88*50101的肽结合分析显示DLA-88*50101衍生的肽与HLA-A*02：01的弱结合，反之亦然。我们的研究结果首次提出了一个详细的肽结合基序的犬MHC I类等位基因产物DLA-88*50101。这些数据支持将狗建立为用于评估和开发基于T细胞的癌症免疫疗法的合适动物模型的目标，使狗和人类患者都受益。
There are limitations in pre-clinical settings using mice as a basis for clinical development in humans. In cancer, similarities exist between humans and dogs; thus, the dog patient can be a link in the transition from laboratory research on mouse models to clinical trials in humans. Knowledge of the peptides presented on MHC molecules is fundamental for the development of highly specific T cell-based immunotherapies. This information is available for human MHC molecules but is absent for the canine MHC. In the present study, we characterized the binding motif of dog leukocyte antigen (DLA) class I allele DLA-88*50101, using human C1R and K562 transfected cells expressing the DLA-88*50101 heavy chain. MHC class I immunoaffinity-purification revealed 3720 DLA-88*50101 derived peptides, which enabled the determination of major anchor positions. The characterized binding motif of DLA-88*50101 was similar to HLA-A*02:01. Peptide binding analyses on HLA-A*02:01 and DLA-88*50101 via flow cytometry showed weak binding of DLA-88*50101 derived peptides to HLA-A*02:01, and vice versa. Our results present for the first time a detailed peptide binding motif of the canine MHC class I allelic product DLA-88*50101. These data support the goal of establishing dogs as a suitable animal model for the evaluation and development of T cell-based cancer immunotherapies, benefiting both dog and human patients.
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影响因子：
56.9
作者：
Frantz, Laurent A. F.;Mullin, Victoria E.;Larson, Greger
通讯作者：
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影响因子：
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作者：
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影响因子：
8.8
作者：
Marchetti, S;Schellens, J H M
通讯作者：
Schellens, J H M