Analysis of Qa-1(b) peptide binding specificity and the capacity of CD94/NKG2A to discriminate between Qa-1-peptide complexes
| Autor: | Kraft, JR, Vance, RE, Pohl, J, Martin, AM, Raulet, DH, Jensen, PE |
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| Rok vydání: | 2000 |
| Předmět: |
1.1 Normal biological development and functioning
Immunology Protein Sorting Signals Inbred C57BL NKG2A Medical and Health Sciences Vaccine Related Mice Immunologic Underpinning research Lectins Biodefense Receptors Killer Cells Animals Antigens Histocompatibility Antigen H-2D Membrane Glycoproteins Binding Sites C-Type Qa-1 Prevention Histocompatibility Antigens Class I H-2 Antigens natural killer cell major histocompatibility complex CD CD94 Natural NK Cell Lectin-Like Receptor Subfamily C NK Cell Lectin-Like Receptor Subfamily D |
| Zdroj: | The Journal of experimental medicine, vol 192, iss 5 |
| Popis: | The major histocompatibility complex class Ib protein, Qa-1(b), serves as a ligand for murine CD94/NKG2A natural killer (NK) cell inhibitory receptors. The Qa-1(b) peptide-binding site is predominantly occupied by a single nonameric peptide, Qa-1 determinant modifier (Qdm), derived from the leader sequence of H-2D and L molecules. Five anchor residues were identified in this study by measuring the peptide-binding affinities of substituted Qdm peptides in experiments with purified recombinant Qa-1(b). A candidate peptide-binding motif was determined by sequence analysis of peptides eluted from Qa-1 that had been folded in the presence of random peptide libraries or pools of Qdm derivatives randomized at specific anchor positions. The results indicate that Qa-1(b) can bind a diverse repertoire of peptides but that Qdm has an optimal primary structure for binding Qa-1(b). Flow cytometry experiments with Qa-1(b) tetramers and NK target cell lysis assays demonstrated that CD94/NKG2A discriminates between Qa-1(b) complexes containing peptides with substitutions at nonanchor positions P4, P5, or P8. Our findings suggest that it may be difficult for viruses to generate decoy peptides that mimic Qdm and raise the possibility that competitive replacement of Qdm with other peptides may provide a novel mechanism for activation of NK cells. |
| Databáze: | OpenAIRE |
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