A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity

Multhoff, Gabriele and Pfister, K. and Gehrmann, M. and Hantschel, M. and Gross, C. and Hafner, M. and Hiddemann, W. (2001) A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity. CELL STRESS & CHAPERONES, 6 (4). pp. 337-344. ISSN 1355-8145

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Abstract

Compared with normal cells, tumor cell lines exhibit an unusual plasma membrane localization of heat shock protein 70 (Hsp70). This tumor-selective Hsp70 membrane expression has been found to correlate with an increased sensitivity to lysis mediated by human natural killer (NK) cells that transiently adhere to plastic following cytokine stimulation. A human Hsp70-specific monoclonal antibody (mAb) detects membrane-bound Hsp70 on viable tumor cells and blocks the immune response of NK cells against Hsp70-expressing tumor cells. By peptide scanning (pep-scan) analysis, the epitope of this mAb was mapped as the C-terminal-localized 8-mer NLLGRFEL (NLL, amino acids [aa] 454-461). Most interestingly, similar to full-length Hsp70 protein, the N-terminal-extended 14-mer peptide TKDNNLLGRFELSG (TKD, aa 450-463) was able to stimulate the cytolytic and proliferative activity of NK cells at concentrations equivalent to full-length Hsp70 protein. Blocking studies revealed that an excess of the 14-mer peptide TKDNNLLGRFELSG inhibits the cytolytic activity of NK cells similar to that of Hsp70 protein. In comparison, other TKD-related peptides, including the 8-mer antibody epitope NLLGRFEL (aa 454-461), the 12-mer TKDNNLLGRFEL (aa 450-461), the 13-mer C-terminal-extended peptide NLLGRFELSGIPP (aa 454-466), the 14-mer TKD-equivalent sequences of Hsp70hom TKDNNLLGRFELTG (aa 450-463), Hsc70 TKDNNLLGKFELTG (aa 450-463), and DnaK AADNKSLGQFNLDG (aa 447-460) failed to activate NK activity.

Item Type: Article
Uncontrolled Keywords: HEAT-SHOCK-PROTEIN; HUMAN TUMOR-CELLS; CYTOTOXIC T-LYMPHOCYTES; SURFACE EXPRESSION; IN-VITRO; ANTIGEN; STRESS; SENSITIVITY; CHAPERONES; RECEPTOR;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 Dec 2021 10:23
Last Modified: 06 Dec 2021 10:23
URI: https://pred.uni-regensburg.de/id/eprint/41056

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