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流行的拳师 MHC 类 I 同种异型犬白细胞抗原 (DLA)-88*034:01 优先结合具有特定基序的九肽。

The prevalent Boxer MHC class Ia allotype dog leukocyte antigen (DLA)-88*034:01 preferentially binds nonamer peptides with a defined motif.

机构信息

Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina.

出版信息

HLA. 2018 Dec;92(6):403-407. doi: 10.1111/tan.13398. Epub 2018 Nov 7.

DOI:10.1111/tan.13398
PMID:30239163
Abstract

Development of effective immunotherapy for chemoresistant malignancies can be advanced by studies in spontaneous cancer models, such as the dog. A crucial first step, T-cell epitope discovery, can be assisted by determination of binding motifs of common dog leukocyte antigen (DLA) class Ia allotypes. Boxers are popular, inbred dogs with increased risks of relevant target cancers and restricted MHC diversity. We sought to identify the motif of DLA-88*034:01, a breed-dominant allotype, to assist peptide prediction from tumor antigens. Mass spectrometry of eluted peptides showed a preference for nonamers with conserved amino acid preferences: basic at position (P)1; hydrophobic at P2; acidic at P4; histidine at P6; and phenylalanine at P9. This data should expedite finding epitopes restricted by this DLA-88 allotype.

摘要

通过对自发性癌症模型(如狗)的研究,可以推进针对耐药性恶性肿瘤的有效免疫疗法的发展。关键的第一步是 T 细胞表位的发现,这可以通过确定常见犬白细胞抗原(DLA)I 类同种异型的结合基序来辅助。拳击犬是一种受欢迎的近交犬种,其相关靶癌症风险增加,且 MHC 多样性受到限制。我们试图确定 DLA-88*034:01 的基序,这是一种品种优势同种异型,以协助从肿瘤抗原中预测肽。洗脱肽的质谱分析显示对具有保守氨基酸偏好的非九肽有偏好:在位置 P1 为碱性;P2 为疏水性;P4 为酸性;P6 为组氨酸;P9 为苯丙氨酸。这些数据应该可以加快找到受这种 DLA-88 同种异型限制的表位。

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1
The prevalent Boxer MHC class Ia allotype dog leukocyte antigen (DLA)-88*034:01 preferentially binds nonamer peptides with a defined motif.流行的拳师 MHC 类 I 同种异型犬白细胞抗原 (DLA)-88*034:01 优先结合具有特定基序的九肽。
HLA. 2018 Dec;92(6):403-407. doi: 10.1111/tan.13398. Epub 2018 Nov 7.
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Dog leukocyte antigen-88*034:01 presents nonamer peptides from canine distemper virus hemagglutinin, large polymerase, and matrix proteins.犬白细胞抗原-88*034:01 呈递来自犬瘟热病毒血凝素、大聚合酶和基质蛋白的九肽。
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引用本文的文献

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Crystal Structure of a Classical MHC Class I Molecule in Dogs; Comparison of DLA-88*0 and DLA-88*5 Category Molecules.犬类经典 MHC I 类分子的晶体结构;DLA-88*0 和 DLA-88*5 类别分子的比较。
Cells. 2023 Apr 6;12(7):1097. doi: 10.3390/cells12071097.
2
Genotyping of canine MHC gene DLA-88 by next-generation sequencing reveals high frequencies of new allele discovery and gene duplication.基于下一代测序技术的犬 MHC 基因 DLA-88 基因型分析揭示了新等位基因发现和基因重复的高频率。
HLA. 2022 Nov;100(5):479-490. doi: 10.1111/tan.14752. Epub 2022 Aug 9.
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Improving human cancer therapy through the evaluation of pet dogs.
通过评估宠物狗来提高人类癌症疗法。
Nat Rev Cancer. 2020 Dec;20(12):727-742. doi: 10.1038/s41568-020-0297-3. Epub 2020 Sep 15.