Identification of Candidate Immunodominant Epitopes and Their HLA-Binding Prediction on BK Polyomavirus Proteins in Healthy Donors

IF 5.9 4区 医学 Q2 CELL BIOLOGY HLA Pub Date : 2024-10-22 DOI:10.1111/tan.15722
Ana Gabriela Lara-de-León, Rut Mora-Buch, Ester Cantó, Cleofé Peña-Gómez, Francesc Rudilla
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Abstract

BK polyomavirus infection is an important cause of graft loss in transplant patients, however, currently available therapies lack effectiveness against this pathogen. Identification of immunological targets for potential treatments is therefore necessary. The aim of this study was to predict candidates of immunodominant epitopes within four BK virus proteins (VP1, VP2, VP3 and LTA) using PBMCs from 44 healthy donors. We used the ELISpot epitope mapping method to evaluate the T-cell response, and HLA-peptide binding was predicted using the NetMHCpan algorithm. A total of 11 potential peptides were selected for VP1, 3 for VP2/VP3 and 13 for LTA. Greater reactivity was observed for VP1 and LTA proteins compared with VP2/VP3. Most of the peptides selected as potential immunodominant candidates were restricted towards several HLA class I and II alleles, with predominant HLA class I binding by computational predictions. Based on these findings, the sequences of the selected immunodominant epitopes candidates and their corresponding HLA restrictions could contribute to the optimisation of functional assays and aid in the design and improvement of immunotherapy strategies against BK virus infections.

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健康捐献者 BK 多瘤病毒蛋白上候选免疫显性表位的鉴定及其 HLA 结合预测
BK 多瘤病毒感染是造成移植患者移植物损失的一个重要原因,但目前可用的疗法对这种病原体缺乏有效性。因此,有必要确定潜在治疗方法的免疫学靶点。本研究的目的是利用 44 名健康捐献者的白细胞介体,预测四种 BK 病毒蛋白(VP1、VP2、VP3 和 LTA)中的免疫优势表位候选。我们使用 ELISpot 表位图法评估 T 细胞反应,并使用 NetMHCpan 算法预测 HLA 与肽的结合。共为 VP1 挑选出 11 个潜在肽,为 VP2/VP3 挑选出 3 个,为 LTA 挑选出 13 个。与 VP2/VP3 蛋白相比,VP1 和 LTA 蛋白的反应性更强。大多数被选为潜在免疫显性候选者的多肽都只与几种 HLA I 类和 II 类等位基因结合,根据计算预测,HLA I 类结合占主导地位。基于这些发现,所选候选免疫优势表位的序列及其相应的 HLA 限制有助于优化功能检测,并有助于设计和改进针对 BK 病毒感染的免疫疗法策略。
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来源期刊
HLA
HLA Immunology and Microbiology-Immunology
CiteScore
3.00
自引率
28.80%
发文量
368
期刊介绍: HLA, the journal, publishes articles on various aspects of immunogenetics. These include the immunogenetics of cell surface antigens, the ontogeny and phylogeny of the immune system, the immunogenetics of cell interactions, the functional aspects of cell surface molecules and their natural ligands, and the role of tissue antigens in immune reactions. Additionally, the journal covers experimental and clinical transplantation, the relationships between normal tissue antigens and tumor-associated antigens, the genetic control of immune response and disease susceptibility, and the biochemistry and molecular biology of alloantigens and leukocyte differentiation. Manuscripts on molecules expressed on lymphoid cells, myeloid cells, platelets, and non-lineage-restricted antigens are welcomed. Lastly, the journal focuses on the immunogenetics of histocompatibility antigens in both humans and experimental animals, including their tissue distribution, regulation, and expression in normal and malignant cells, as well as the use of antigens as markers for disease.
期刊最新文献
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