小柯机器人

美国麻省理工学院和哈佛大学布罗德研究所Daniel B. Graham和Ramnik J. Xavier共同合作，近期取得重要工作进展。他们研究提出利用HLA-II免疫肽谱分析和深度学习来揭示抗原性特征并为抗原发现提供信息。相关研究成果2023年6月9日在线发表于《免疫》杂志上。

据介绍，CD4⁺ T细胞反应具有很强的抗原特异性，并针对抗原呈递细胞上人类白细胞抗原II类（HLA-II）展示的肽表位。配体数据库中不同等位基因的代表性不足，以及对影响体内抗原呈递的因素的不完全理解，限制了肽免疫原性原理的定义。

研究人员使用单等位基因免疫肽组学来鉴定358024个HLA-II结合物，特别关注HLA-DQ和HLA-DP。研究人员发现了一系列结合亲和力和结构抗原特征富集的肽结合模式。这些方面支持了T细胞抗原环境感知预测器（CAPTAn）的开发，这是一种深度学习模型，基于肽抗原对HLA-II的亲和力及其源蛋白的全序列来预测肽抗原。CAPTAn在发现人类微生物组中细菌的流行T细胞表位，和严重急性呼吸系统综合征冠状病毒2型的泛变体表位方面发挥了重要作用。

总之，CAPTAn和相关数据集为抗原发现和HLA等位基因与免疫病理的遗传关联提供了资源。

附：英文原文

Title: HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery

Author: Martin Straar, Jihye Park, Jennifer G. Abelin, Hannah B. Taylor, Thomas K. Pedersen, Damian R. Plichta, Eric M. Brown, Basak Eraslan, Yuan-Mao Hung, Kayla Ortiz, Karl R. Clauser, Steven A. Carr, Ramnik J. Xavier, Daniel B. Graham

Issue&Volume: 2023-06-09

Abstract: CD4+ T cell responses are exquisitely antigen specific and directed toward peptideepitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presentingcells. Underrepresentation of diverse alleles in ligand databases and an incompleteunderstanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, weemployed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with aparticular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns acrossa spectrum of binding affinities and enrichment of structural antigen features. Theseaspects underpinned the development of context-aware predictor of T cell antigens(CAPTAn), a deep learning model that predicts peptide antigens based on their affinityto HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discoveringprevalent T cell epitopes from bacteria in the human microbiome and a pan-variantepitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resourcefor antigen discovery and the unraveling genetic associations of HLA alleles withimmunopathologies.

DOI: 10.1016/j.immuni.2023.05.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00226-1

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