Functional analysis of the molecular factors controlling Qa1-mediated protection of target cells from NK lysis
| Autor: | Colin G. Brooks, Frances Gays, P. J. Dyson, Jennifer A. Toomey, Millrain Mm, Karen P. Fraser, AG Diamond |
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| Rok vydání: | 2001 |
| Předmět: |
Cytotoxicity
Immunologic Immunology Biology Protein Sorting Signals NKG2 Transfection Natural killer cell Cell Line Mice Fetus L Cells Antigen Species Specificity Antigens CD medicine Tumor Cells Cultured Immunology and Allergy Animals Humans Lectins C-Type Receptors Immunologic Receptor Membrane Glycoproteins Histocompatibility Antigens Class I Temperature Cytotoxicity Tests Immunologic Peptide Fragments Cell biology Killer Cells Natural Mice Inbred C57BL Receptors Antigen medicine.anatomical_structure Cell culture Receptors Natural Killer Cell ATP-Binding Cassette Transporters NK Cell Lectin-Like Receptor Subfamily C Peptides NK Cell Lectin-Like Receptor Subfamily D Protein Binding |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 166(3) |
| ISSN: | 0022-1767 |
| Popis: | CD94/NKG2 receptors on mouse NK cells recognize the nonclassical class I molecule Qa1 and can deliver inhibitory signals that prevent NK cells from lysing Qa1-expressing cells. However, the exact circumstances under which Qa1 protects cells from NK lysis and, in particular, the role of the dominant Qa1-associated peptide, Qdm, are unclear. In this study, we examined in detail the lysis of Qa1-expressing cells by fetal NK cells that express CD94/NKG2 receptors for Qa1 but that lack receptors for classical class I molecules. Whereas mouse L cells and human C1R cells transfected with Qa1 were resistant to lysis by these effectors, Qa1-transfected TAP-deficient human T2 cells showed no resistance despite expressing high levels of surface Qa1. However, these cells could be efficiently protected by exposure to low concentrations of Qdm peptide or certain Qdm-related peptides. By contrast, even prolonged exposure of TAP-deficient RMA/S cells to high doses of Qdm peptide failed to induce levels of surface Qa1 detectable with a Qa1-specific mAb or to protect them from NK lysis, although such treatment induced sensitivity to lysis by Qa1-specific CTL. Collectively, these findings indicate that high surface expression of Qa1 is necessary but not sufficient for protection, and that effective protection requires the expression of sufficient levels of suitable Qa1-peptide complexes to overcome activatory signals. Results obtained with a series of substituted Qdm peptides suggest that residues at positions 3, 4, 5, and 8 of the Qdm sequence, AMAPRTLLL, are important for recognition of Qa1-Qdm complexes by inhibitory CD94/NKG2 receptors. |
| Databáze: | OpenAIRE |
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