Footprints of antigen processing boost MHC class II natural ligand predictions

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt


  • Carolina Barra
  • Bruno Alvarez
  • Sinu Paul
  • Alessandro Sette
  • Bjoern Peters
  • Massimo Andreatta
  • Buus, Søren
  • Morten Nielsen

BACKGROUND: Major histocompatibility complex class II (MHC-II) molecules present peptide fragments to T cells for immune recognition. Current predictors for peptide to MHC-II binding are trained on binding affinity data, generated in vitro and therefore lacking information about antigen processing. METHODS: We generate prediction models of peptide to MHC-II binding trained with naturally eluted ligands derived from mass spectrometry in addition to peptide binding affinity data sets. RESULTS: We show that integrated prediction models incorporate identifiable rules of antigen processing. In fact, we observed detectable signals of protease cleavage at defined positions of the ligands. We also hypothesize a role of the length of the terminal ligand protrusions for trimming the peptide to the MHC presented ligand. CONCLUSIONS: The results of integrating binding affinity and eluted ligand data in a combined model demonstrate improved performance for the prediction of MHC-II ligands and T cell epitopes and foreshadow a new generation of improved peptide to MHC-II prediction tools accounting for the plurality of factors that determine natural presentation of antigens.

TidsskriftGenome Medicine
Antal sider15
StatusUdgivet - 2018

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