التفاصيل البيبلوغرافية
| العنوان: |
Diversity of Natural Self-Derived Ligands Presented by Different HLA Class I Molecules in Transporter Antigen Processing-Deficient Cells. |
| المؤلفون: |
Lorente, Elena, Infantes, Susana, Barnea, Eilon, Beer, Ilan, Barriga, Alejandro, García-Medel, Noel, Lasala, Fátima, Jiménez, Mercedes, Admon, Arie, López, Daniel |
| المصدر: |
PLoS ONE; Mar2013, Vol. 8 Issue 3, p1-10, 10p |
| مصطلحات موضوعية: |
HLA histocompatibility antigens, BIODIVERSITY, LIGANDS (Biochemistry), CYTOSOL, ENDOPLASMIC reticulum, GENE expression, MASS spectrometry, PROTEOLYSIS, CARRIER proteins |
| مستخلص: |
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 P1 position of the scissile bond was found for the TAP-independent ligands. These data draw a new and intricate picture of TAP-independent pathways. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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