Deciphering the landscape of phosphorylated HLA-II ligands

Marthe Solleder; Julien Racle; Philippe Guillaume; George Coukos; Michal Bassani-Sternberg; David Gfeller

doi:10.1016/j.isci.2022.104215

Deciphering the landscape of phosphorylated HLA-II ligands

iScience. 2022 Apr 6;25(5):104215. doi: 10.1016/j.isci.2022.104215. eCollection 2022 May 20.

Authors

Marthe Solleder^{1

2}, Julien Racle^{1

2}, Philippe Guillaume¹, George Coukos^{1

3}, Michal Bassani-Sternberg^{1

3}, David Gfeller^{1

2}

Affiliations

¹ Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland.
² Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland.
³ Department of Oncology, University Hospital of Lausanne (CHUV), 1011 Lausanne, Switzerland.

Abstract

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.

Keywords: Cell biology; Immunology; Omics.