Solleder Marthe, Racle Julien, Guillaume Philippe, Coukos George, Bassani-Sternberg Michal, Gfeller David
Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland.
Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland.
iScience. 2022 Apr 6;25(5):104215. doi: 10.1016/j.isci.2022.104215. eCollection 2022 May 20.
CD4 T cell activation in infectious diseases and cancer is governed by the recognition of peptides presented on class II human leukocyte antigen (HLA-II) molecules. Therefore, HLA-II ligands represent promising targets for vaccine design and personalized cancer immunotherapy. Much work has been done to identify and predict unmodified peptides presented on HLA-II molecules. However, little is known about the presentation of phosphorylated HLA-II ligands. Here, we analyzed Mass Spectrometry HLA-II peptidomics data and identified 1,943 unique phosphorylated HLA-II ligands. This enabled us to precisely define phosphorylated binding motifs for more than 30 common HLA-II alleles and to explore various molecular properties of phosphorylated peptides. Our data were further used to develop the first predictor of phosphorylated peptide presentation on HLA-II molecules.
传染性疾病和癌症中CD4 T细胞的激活受II类人类白细胞抗原（HLA-II）分子所呈递肽段的识别所调控。因此，HLA-II配体是疫苗设计和个性化癌症免疫疗法的有前景的靶点。在识别和预测HLA-II分子上呈递的未修饰肽段方面已经开展了大量工作。然而，对于磷酸化HLA-II配体的呈递了解甚少。在此，我们分析了质谱HLA-II肽组学数据，并鉴定出1943个独特的磷酸化HLA-II配体。这使我们能够精确界定30多种常见HLA-II等位基因的磷酸化结合基序，并探索磷酸化肽段的各种分子特性。我们的数据进一步用于开发首个预测HLA-II分子上磷酸化肽段呈递情况的预测工具。
