Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6586
Diversity of natural self-derived ligands presented by different HLA class I molecules in transporter antigen processing-deficient cells
PLoS One. 2013;8(3):e59118.
The transporter associated with antigen processing (TAP) translocates the cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen where they complex with nascent human leukocyte antigen (HLA) class I molecules. Non-functional TAP complexes and viral or tumoral blocking of these transporters leads to reduced HLA class I surface expression and a drastic change in the available peptide repertoire. Using mass spectrometry to analyze complex human leukocyte antigen HLA-bound peptide pools isolated from large numbers of TAP-deficient cells, we identified 334 TAP-independent ligands naturally presented by four different HLA-A, -B, and -C class I molecules with very different TAP dependency from the same cell line. The repertoire of TAP-independent peptides examined favored increased peptide lengths and a lack of strict binding motifs for all four HLA class I molecules studied. The TAP-independent peptidome arose from 182 parental proteins, the majority of which yielded one HLA ligand. In contrast, TAP-independent antigen processing of very few cellular proteins generated multiple HLA ligands. Comparison between TAP-independent peptidome and proteome of several subcellular locations suggests that the secretory vesicle-like organelles could be a relevant source of parental proteins for TAP-independent HLA ligands. Finally, a predominant endoproteolytic peptidase specificity for Arg/Lys or Leu/Phe residues in the P(1) position of the scissile bond was found for the TAP-independent ligands. These data draw a new and intricate picture of TAP-independent pathways.
Antigen Presentation | Cell Line, Tumor | Cytosol | Endoplasmic Reticulum | Genetic Variation | Humans | Mass Spectrometry | Peptides | Proteolysis | ATP-Binding Cassette Transporters | HLA-A Antigens | HLA-B Antigens | HLA-C Antigens | Ligands | Hybridomas
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