Advanced & Cell Therapy Services, Banc de Sang i Teixits (Blood and Tissue Bank, BST), Barcelona, Spain.
Transfusional Medicine Group, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain.
HLA. 2024 Oct;104(4):e15722. doi: 10.1111/tan.15722.
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.
BK 多瘤病毒感染是移植患者移植物丢失的重要原因，然而，目前可用的治疗方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靶标。本研究旨在使用 44 名健康供体的 PBMC，通过 ELISpot 表位作图方法来预测 4 种 BK 病毒蛋白（VP1、VP2、VP3 和 LTA）中的免疫优势表位候选物。我们使用 ELISpot 表位作图方法来评估 T 细胞反应，使用 NetMHCpan 算法预测 HLA-肽结合。总共选择了 11 个 VP1 蛋白的潜在肽，3 个 VP2/VP3 蛋白的潜在肽和 13 个 LTA 蛋白的潜在肽。与 VP2/VP3 相比，VP1 和 LTA 蛋白表现出更强的反应性。所选潜在免疫优势候选物的大多数肽受到几种 HLA Ⅰ类和Ⅱ类等位基因的限制，计算预测表明主要与 HLA Ⅰ类结合。基于这些发现，所选免疫优势表位候选物的序列及其相应的 HLA 限制可有助于优化功能测定，并有助于设计和改进针对 BK 病毒感染的免疫治疗策略。
