Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells

• Published in: PloS one 2019-01, Vol.14 (1), p.e0210583-e0210583
• Main Authors: Martín-Galiano, Antonio J, López, Daniel
• Format: Article
• Language: English
• Subjects: Antigen presentation; Antigen Presentation - immunology; Antigen processing; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Arthritis; ATP-Binding Cassette Transporters - immunology; ATP-Binding Cassette Transporters - metabolism; Bioinformatics; Biology and Life Sciences; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell surface; Computational Biology - methods; Computer applications; Cytosol; Datasets; Endoplasmic reticulum; Endoplasmic Reticulum - immunology; Endoplasmic Reticulum - metabolism; Glycine; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Humans; Immune system; Ligands; Major histocompatibility complex; Mass spectrometry; Mass spectroscopy; Medicine and Health Sciences; Membrane proteins; Metabolism; Peptides; Peptides - immunology; Peptides - metabolism; Proline; Protein Transport; Proteins; Proteolysis; Proteomes; Proteomics; Proteomics - methods; Ribonucleic acid; RNA; Scientific imaging; Studies; TAP protein; Translocation; Transporter; Viral infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0210583

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.