巨细胞病毒 pp65 抗原的预测与实际识别的 CD8+ T 细胞表位之间的差异与偶然表位优势。

Discordance Between the Predicted Versus the Actually Recognized CD8+ T Cell Epitopes of HCMV pp65 Antigen and Aleatory Epitope Dominance.

机构信息

Research and Development, Cellular Technology Ltd., Shaker Heights, OH, United States.

Laboratorio de Inmunomedicina & Inmunoinformatica, Departamento de Immunologia & O2, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.

出版信息

Front Immunol. 2021 Feb 9;11:618428. doi: 10.3389/fimmu.2020.618428. eCollection 2020.

Abstract

CD8+ T cell immune monitoring aims at measuring the size and functions of antigen-specific CD8+ T cell populations, thereby providing insights into cell-mediated immunity operational in a test subject. The selection of peptides for CD8+ T cell detection is critical because within a complex antigen exists a multitude of potential epitopes that can be presented by HLA class I molecules. Further complicating this task, there is HLA class I polygenism and polymorphism which predisposes CD8+ T cell responses towards individualized epitope recognition profiles. In this study, we compare the actual CD8+ T cell recognition of a well-characterized model antigen, human cytomegalovirus (HCMV) pp65 protein, with its anticipated epitope coverage. Due to the abundance of experimentally defined HLA-A02:01-restricted pp65 epitopes, and because epitope predictions are most advanced for HLA-A02:01, we elected to focus on subjects expressing this allele. In each test subject, every possible CD8+ T cell epitope was systematically covered testing 553 individual peptides that walk the sequence of pp65 in steps of single amino acids. Highly individualized CD8+ T cell response profiles with aleatory epitope recognition patterns were observed. No correlation was found between epitopes' ranking on the prediction scale and their actual immune dominance. Collectively, these data suggest that accurate CD8+ T cell immune monitoring may necessitate reliance on agnostic mega peptide pools, or brute force mapping, rather than electing individual peptides as representative epitopes for tetramer and other multimer labeling of surface antigen receptors.

摘要

CD8+ T 细胞免疫监测旨在测量抗原特异性 CD8+ T 细胞群体的大小和功能,从而深入了解测试对象中细胞介导的免疫作用。选择用于 CD8+ T 细胞检测的肽类是至关重要的,因为在复杂的抗原中存在许多潜在的表位,可以由 HLA Ⅰ类分子呈递。进一步使这项任务复杂化的是 HLA Ⅰ类多态性和多态性,这使 CD8+ T 细胞反应倾向于个体化表位识别谱。在这项研究中,我们将对一个经过充分研究的模型抗原,即人类巨细胞病毒(HCMV)pp65 蛋白的实际 CD8+ T 细胞识别与预期的表位覆盖进行比较。由于实验定义的 HLA-A02:01 限制性 pp65 表位丰富,并且由于 HLA-A02:01 的表位预测最为先进,我们选择专注于表达这种等位基因的受试者。在每个测试对象中,通过对 pp65 序列进行单次氨基酸步长的 553 个单个肽进行系统测试,全面覆盖了每个可能的 CD8+ T 细胞表位。观察到高度个体化的 CD8+ T 细胞反应谱,具有任意表位识别模式。在预测尺度上的表位排名与实际免疫优势之间没有相关性。总的来说,这些数据表明,准确的 CD8+ T 细胞免疫监测可能需要依赖于不可知的大型肽库,或者进行强制性映射,而不是选择单个肽作为四聚体和其他表面抗原受体多聚体标记的代表性表位。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60ce/7900545/0005bc327b98/fimmu-11-618428-g001.jpg

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