Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/8692
Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells
PLoS One. 2019 Jan 15;14(1):e0210583.
The transporter associated with antigen processing (TAP) is a key element of the major histocompatibility complex (MHC) class I antigen processing and presentation pathway. Nonfunctional TAP complexes impair the translocation of cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen. This drastic reduction in the available peptide repertoire leads to a significant decrease in MHC class I cell surface expression. Using mass spectrometry, different studies have analyzed the cellular MHC class I ligandome from TAP-deficient cells, but the analysis of the parental proteins, the source of these ligands, still deserves an in-depth analysis. In the present report, several bioinformatics protocols were applied to investigate the nature of parental proteins for the previously identified TAP-independent MHC class I ligands. Antigen processing in TAP-deficient cells mainly focused on small, abundant or highly integral transmembrane proteins of the cellular proteome. This process involved abundant proteins of the central RNA metabolism. In addition, TAP-independent ligands were preferentially cleaved from the N- and C-terminal ends with respect to the central regions of the parental proteins. The abundance of glycine, proline and aromatic residues in the C-terminal sequences from TAP-independently processed proteins allows the accessibility and specificity required for the proteolytic activities that generates the TAP-independent ligandome. This limited proteolytic activity towards a set of preferred proteins in a TAP-negative environment would therefore suffice to promote the survival of TAP-deficient individuals.
ATP-Binding Cassette Transporters | Antigen Presentation | Antigen-Presenting Cells | CD8-Positive T-Lymphocytes | Computational Biology | Endoplasmic Reticulum | Histocompatibility Antigens Class I | Humans | Ligands | Peptides | Protein Transport | Proteomics
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