The cell surface-localized heat shock protein 70 epitope TKD induces migration and cytolytic activity selectively in human NK cells.
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.
Gastpar
Robert
R
Department of Hematology and Oncology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, D-93053 Regensburg, Germany.
Gross
Catharina
C
Rossbacher
Lydia
L
Ellwart
Joachim
J
Riegger
Julia
J
Multhoff
Gabriele
G
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D020816:Amino Acid Motifs; D015703:Antigens, CD / Q000096:biosynthesis; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D002474:Cell-Free System / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments / Q000502:physiology*
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D017252:CD3 Complex; D019002:CD56 Antigen; D018840:HSP70 Heat-Shock Proteins; D016056:Immunodominant Epitopes; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments