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The cell surface-localized heat shock protein 70 epitope TKD induces migration and cytolytic activity selectively in human NK cells.
J. Immunol. 172, 972-980 (2004)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
NATURAL-KILLER-CELLS; SEVERE COMBINED IMMUNODEFICIENCY; HEAT-SHOCK-PROTEIN; TUMOR-NECROSIS-FACTOR; RECEPTORS; HSP70; LIVER; EXPRESSION; MICE; RECOGNITION
ISSN (print) / ISBN
0022-1767
e-ISSN
1550-6606
Journal
Journal of Immunology
Quellenangaben
Volume: 172,
Issue: 2,
Pages: 972-980
Publisher
American Association of Immunologists
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)