Chan Queenie W T, Baker Teesha C, Kuan Chia-Wei, Song Lucy, Yu Hongbing, Foster Leonard J
Department of Biochemistry & Molecular Biology, Michael Smith Laboratories, and Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
PLoS One. 2025 Sep 25;20(9):e0332950. doi: 10.1371/journal.pone.0332950. eCollection 2025.
The goal in vaccinology is to identify candidate antigens for clinical trials that will elicit an immune response for a significant portion of the target population. Unfortunately, promising data generated at the preclinical level often cannot be replicated in larger sample sizes. The goal of this project was to develop a methodology for processing MAE-generated data to identify MHC epitopes, minimize non-specific contaminants, find binding motifs, and utilize genetic connections among donors to determine which peptides were presented by specific MHC alleles.
Our approach demonstrated that mild acid elution of peptides from seven consanguineous B-lymphocyte lines accurately reflects the HLA genotypes within family members, highlighting the specificity of MAE. Additionally, the data successfully reproduced known MHC binding motifs and partially deconvoluted the originating HLA alleles of the epitopes.
These findings suggest that our approach could be applied to numerous cell lines globally to evaluate a wide array of HLA haplotypes. This may help to reveal candidate vaccine antigens that induce immune protection for a wider population.
疫苗学的目标是识别用于临床试验的候选抗原,这些抗原能在很大一部分目标人群中引发免疫反应。不幸的是,临床前阶段产生的有前景的数据往往无法在更大样本量中复制。本项目的目标是开发一种处理MAE生成数据的方法,以识别MHC表位、尽量减少非特异性污染物、找到结合基序,并利用供体之间的遗传联系来确定哪些肽由特定的MHC等位基因呈递。
我们的方法表明,从七个近亲B淋巴细胞系中温和酸洗脱肽准确反映了家庭成员中的HLA基因型,突出了MAE的特异性。此外,数据成功再现了已知的MHC结合基序,并部分解卷积了表位的起源HLA等位基因。
这些发现表明,我们的方法可应用于全球众多细胞系,以评估多种HLA单倍型。这可能有助于揭示能为更广泛人群诱导免疫保护的候选疫苗抗原。