Abstract
Profiling of surface-bound proteins uncovers a tumor-selective heat shock protein 70 (Hsp70) membrane expression that provides a target structure for human NK cells. Hsp70 peptide TKD (TKDNNLLGRFELSG; aa 450-463) was found to enhance the cytolytic activity of NK cells. In this study, we demonstrate that TKD-activated CD3-CD56+CD94+ NK cells are selectively attracted by Hsp70 membrane-positive tumor cells, and supernatants derived thereof. Hsp70 membrane-negative tumors failed to attract these NK cells. The capacity to migrate was associated with a substantial lytic activity against Hsp70-positive tumor cells. Because NK cell migration was independent of cell-to-cell contact, the involvement of a soluble factor was assumed. Interestingly, synthetic Hsp70 protein and Hsp70 peptide TKD, mimicking surface-bound Hsp70, initiates migration of NK cells in a concentration-dependent (1-5 microg/ml), highly selective, and chemokine-independent manner. In summary, our results indicate that Hsp70 peptide TKD not only stimulates cytolysis but also chemotaxis in CD3-CD56+CD94+ NK cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / biosynthesis
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / physiology
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Amino Acid Motifs
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Antigens, CD / biosynthesis
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CD3 Complex / metabolism
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CD56 Antigen / biosynthesis
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Cell Line, Tumor
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Cell Membrane / pathology
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Cell Movement / immunology*
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Cell-Free System / immunology
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Cell-Free System / pathology
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Cells, Cultured
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Cytotoxicity Tests, Immunologic
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Cytotoxicity, Immunologic / immunology*
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HSP70 Heat-Shock Proteins / biosynthesis
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HSP70 Heat-Shock Proteins / metabolism
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HSP70 Heat-Shock Proteins / physiology*
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Humans
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Immunodominant Epitopes / biosynthesis
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Immunodominant Epitopes / metabolism
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Immunodominant Epitopes / physiology*
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism*
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Lectins, C-Type / biosynthesis
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / immunology
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Lymphocyte Activation / immunology
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NK Cell Lectin-Like Receptor Subfamily D
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Peptide Fragments / physiology*
Substances
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Adjuvants, Immunologic
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Antigens, CD
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CD3 Complex
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CD56 Antigen
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HSP70 Heat-Shock Proteins
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Immunodominant Epitopes
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KLRD1 protein, human
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Lectins, C-Type
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NK Cell Lectin-Like Receptor Subfamily D
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Peptide Fragments