An Hsp70 peptide initiates NK cell killing of leukemic blasts after stem cell transplantation

Leuk Res. 2008 Apr;32(4):527-34. doi: 10.1016/j.leukres.2007.03.027. Epub 2007 May 31.

Abstract

In contrast to solid tumors, leukemic blasts frequently present both Hsp70 and HLA-E on their cell surface and thereby present activating and inhibitory signals to CD94(+) NK cells. In the first 12 months after stem cell transplantation (SCT) CD94(+) NK cells clearly dominate over CD3(+)/CD16(-)/56(-) T and CD3(+)/CD16(+)/56(+) NK-like T cells. An incubation of post-SCT-derived peripheral blood lymphocytes with the Hsp70 peptide TKD and IL-15 enhances the cell surface density of CD56/CD94 and initiates the cytolytic activity of NK cells against Hsp70/HLA-E double-positive autologous and allogeneic leukemic blasts. Hsp70 was identified as the target structure for TKD-activated NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Cytotoxicity, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • HLA Antigens / physiology
  • HSP70 Heat-Shock Proteins / physiology*
  • Histocompatibility Antigens Class I / physiology
  • Humans
  • Interleukin-15 / metabolism
  • Killer Cells, Natural / immunology*
  • Leukemia / immunology
  • Leukemia / pathology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Middle Aged
  • Peptide Fragments / physiology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Stem Cell Transplantation*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • HLA Antigens
  • HLA-E antigen
  • HSP70 Heat-Shock Proteins
  • Histocompatibility Antigens Class I
  • Interleukin-15
  • Peptide Fragments