Deciphering the landscape of phosphorylated HLA-II ligands
Marthe Solleder,
Julien Racle,
Philippe Guillaume,
George Coukos,
Michal Bassani-Sternberg,
David Gfeller
Affiliations
Marthe Solleder
Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland
Julien Racle
Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland
Philippe Guillaume
Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland
George Coukos
Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Department of Oncology, University Hospital of Lausanne (CHUV), 1011 Lausanne, Switzerland
Michal Bassani-Sternberg
Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Department of Oncology, University Hospital of Lausanne (CHUV), 1011 Lausanne, Switzerland; Corresponding author
David Gfeller
Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland; Corresponding author
Summary: 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.
