Increased diversity of the HLA-B40 ligandome by the presentation of peptides phosphorylated at their main anchor residue.

Molecular & Cellular Proteomics : MCP
Miguel MarcillaJuan Pablo Albar

Abstract

Human leukocyte antigen (HLA) class I molecules bind peptides derived from the intracellular degradation of endogenous proteins and present them to cytotoxic T lymphocytes, allowing the immune system to detect transformed or virally infected cells. It is known that HLA class I-associated peptides may harbor posttranslational modifications. In particular, phosphorylated ligands have raised much interest as potential targets for cancer immunotherapy. By combining affinity purification with high-resolution mass spectrometry, we identified more than 2000 unique ligands bound to HLA-B40. Sequence analysis revealed two major anchor motifs: aspartic or glutamic acid at peptide position 2 (P2) and methionine, phenylalanine, or aliphatic residues at the C terminus. The use of immobilized metal ion and TiO2 affinity chromatography allowed the characterization of 85 phosphorylated ligands. We further confirmed every sequence belonging to this subset by comparing its experimental MS2 spectrum with that obtained upon fragmentation of the corresponding synthetic peptide. Remarkably, three phospholigands lacked a canonical anchor residue at P2, containing phosphoserine instead. Binding assays showed that these peptides bound to HLA-B40 with h...Continue Reading

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Citations

May 8, 2016·Current Opinion in Immunology·Michal Bassani-Sternberg, George Coukos
Dec 7, 2016·Molecular & Cellular Proteomics : MCP·Adán AlpízarMiguel Marcilla
Aug 7, 2018·Expert Review of Proteomics·Sri H RamarathinamAnthony W Purcell
Nov 9, 2018·Immunology·Anna Mestre-FerrerIñaki Alvarez
Sep 19, 2019·Molecular & Cellular Proteomics : MCP·Elena LorenteJosé A López de Castro
Dec 19, 2019·Molecular & Cellular Proteomics : MCP·Marthe SollederDavid Gfeller
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Apr 24, 2019·Diabetes·Anthony W PurcellTeresa P DiLorenzo
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Dec 3, 2015·Molecular & Cellular Proteomics : MCP·Etienne CaronRuedi Aebersold
Nov 21, 2019·Molecular & Cellular Proteomics : MCP·Juan Antonio VizcaínoEtienne Caron
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Marthe SollederDavid Gfeller
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Juan Antonio VizcaínoEtienne Caron
Nov 1, 2019·Molecular & Cellular Proteomics : MCP·Elena LorenteJosé A López de Castro

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